tbuckley/cabot-search huggingface dataset:
Immune cell–derived opioids protect against neuropathic pain in mice
Authors: Dominika Labuz, Yvonne Schmidt, Anja Schreiter, Heike L. Rittner, Shaaban A. Mousa, Halina Machelska
Journal: Journal of Clinical Investigation (2009)

The analgesic effects of leukocyte-derived opioids have been exclusively demonstrated for somatic inflammatory pain, for example, the pain associated with surgery and arthritis. Neuropathic pain results from injury to nerves, is often resistant to current treatments, and can seriously impair a patient's quality of life. Although it has been recognized that neuronal damage can involve inflammation, it is generally assumed that immune cells act predominately as generators of neuropathic pain. However, in this study we have demonstrated that leukocytes containing opioids are essential regulators of pain in a mouse model of neuropathy. About 30%-40% of immune cells that accumulated at injured nerves expressed opioid peptides such as beta-endorphin, Met-enkephalin, and dynorphin A. Selective stimulation of these cells by local application of corticotropin-releasing factor led to opioid peptide-mediated activation of opioid receptors in damaged nerves. This ultimately abolished tactile allodynia, a highly debilitating heightened response to normally innocuous mechanical stimuli, which is symptomatic of neuropathy. Our findings suggest that selective targeting of opioid-containing immune cells promotes endogenous pain control and offers novel opportunities for management of painful neuropathies.
A Mass Balance and Disposition Study of the DNA Methyltransferase Inhibitor Zebularine (NSC 309132) and Three of Its Metabolites in Mice
Authors: Jan H. Beumer, Erin Joseph, Merrill J. Egorin, Robert S. Parker, David Z. D'argenio, Joseph M. Covey, Julie L. Eiseman
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To elucidate the in vivo metabolic fate of zebularine (NSC 309132), a DNA methyltransferase inhibitor proposed for clinical evaluation in the treatment of cancer. Experimental Design: Male, CD2F1 mice were dosed i.v. with 100 mg/kg 2-[14C]zebularine. At specified times between 5 and 1,440 minutes, mice were euthanized. Plasma, organs, carcass, urine, and feces were collected and assayed for total radioactivity. Plasma and urine were also analyzed for zebularine and its metabolites with a previously validated high-pressure liquid chromatography assay. A similar experiment was done with 2-[14C]uridine, the proposed primary metabolite of zebularine. Results: Maximum plasma concentrations were 462, 306, 33.6, 21.7, and 11.5 μmol/L for total radioactivity, zebularine, uridine, uracil (each at 5 minutes), and dihydrouracil (at 15 minutes), respectively. Total radioactivity, zebularine, uridine, uracil, and dihydrouracil were rapidly eliminated from plasma, and after 45 minutes, none of the individual compounds could be quantitated by high-pressure liquid chromatography. Plasma data were consistent with sequential conversion of zebularine to uridine, uracil, and dihydrouracil. 2-Pyrimidinone was not observed. Prolonged retention of radioactivity, at concentrations higher than in plasma, was observed in tissues. Recovery of given radioactivity in urine (30.3% of dose), feces (0.4% of dose), cage wash (7.9% of dose), and tissues and carcass (6.1% of dose) after 24 hours implied that up to 55% of radioactivity was expired as 14CO2. Comparison of zebularine and uridine pharmacokinetic data indicated that ∼40% of the zebularine dose was converted to uridine. Conclusions: Zebularine is extensively and rapidly metabolized into endogenous compounds that are unlikely to have effects at the concentrations observed.
Id1-Induced IGF-II and Its Autocrine/Endocrine Promotion of Esophageal Cancer Progression and Chemoresistance—Implications for IGF-II and IGF-IR–Targeted Therapy
Authors: Bin Li, Sai Wah Tsao, Kwok Wah Chan, Dale L. Ludwig, Ruslan Novosyadlyy, Yuk Yin Li, Qing Yu He, Annie L.M. Cheung
Journal: Clinical Cancer Research (2014)

To investigate the autocrine/endocrine role of Id1-induced insulin-like growth factor-II (IGF-II) in esophageal cancer, and evaluate the potential of IGF-II- and IGF-type I receptor (IGF-IR)-targeted therapies.Antibody array-based screening was used to identify differentially secreted growth factors from Id1-overexpressing esophageal cancer cells. In vitro and in vivo assays were performed to confirm the induction of IGF-II by Id1, and to study the autocrine and endocrine effects of IGF-II in promoting esophageal cancer progression. Human esophageal cancer tissue microarray was analyzed for overexpression of IGF-II and its correlation with that of Id1 and phosphorylated AKT (p-AKT). The efficacy of intratumorally injected IGF-II antibody and intraperitoneally injected cixutumumab (fully human monoclonal IGF-IR antibody) was evaluated using in vivo tumor xenograft and experimental metastasis models.Id1 overexpression induced IGF-II secretion, which promoted cancer cell proliferation, survival, and invasion by activating AKT in an autocrine manner. Overexpression of IGF-II was found in 21 of 35 (60%) esophageal cancer tissues and was associated with upregulation of Id1 and p-AKT. IGF-II secreted by Id1-overexpressing esophageal cancer xenograft could instigate the growth of distant esophageal tumors, as well as promote metastasis of circulating cancer cells. Targeting IGF-II and IGF-IR had significant suppressive effects on tumor growth and metastasis in mice. Cixutumumab treatment enhanced the chemosensitivity of tumor xenografts to fluorouracil and cisplatin.The Id1-IGF-II-IGF-IR-AKT signaling cascade plays an important role in esophageal cancer progression. Blockade of IGF-II/IGF-IR signaling has therapeutic potential in the management of esophageal cancer.
Does passive smoking increase the frequency of health service contacts in children with asthma?
Authors: I K Crombie
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Passive smoking is a major cause of respiratory morbidity in children. However, few studies give accurate estimates of the health effects of passive smoking in children with asthma using an objective measure of exposure. The effects of passive smoking using salivary cotinine levels to measure exposure were investigated. <h3>METHODS</h3> A sample of 438 children aged 2–12 years with asthma who had a parent who smoked were recruited in Tayside and Fife, Scotland. Health service contacts for asthma, assessed from GP case records, were used as a proxy for morbidity. <h3>RESULTS</h3> A weak U-shaped relationship was found between the salivary cotinine level and health service contacts for asthma: compared with low cotinine levels those with moderate cotinine levels had a reduced contact rate (relative rate (RR) = 0.91, 95% confidence interval (CI) 0.80 to 1.05), whereas high cotinine levels were associated with an increased rate of contact (RR = 1.19, 95% CI 1.05 to 1.37). In contrast, a strong association was seen with the amount the parent reported smoking in front of the child: the higher the level the fewer visits were made for asthma (RR for everyday exposure = 0.66, 95% CI 0.56 to 0.77). This effect was not seen for non-respiratory visits. Demographic factors, age of child, and number of children in the family all had a powerful effect on the number of visits for asthma. The parents9 perception of asthma severity was associated with visit frequency independent of actual severity (derived from drug treatment). <h3>CONCLUSION</h3> High levels of parental smoking in the home are associated with a reduction in health care contacts for asthma. This could be due to a lack of awareness of asthma symptoms among heavy smokers or a reluctance to visit the GP. Children with asthma who have parents who smoke heavily may not be receiving adequate management.
Probiotic Prophylaxis of Ventilator-associated Pneumonia
Authors: Lee E. Morrow, Marin H. Kollef, Thomas B. Casale
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Enteral administration of probiotics may modify the gastrointestinal environment in a manner that preferentially favors the growth of minimally virulent species. It is unknown whether probiotic modification of the upper aerodigestive flora can reduce nosocomial infections.To determine whether oropharyngeal and gastric administration of Lactobacillus rhamnosus GG can reduce the incidence of ventilator-associated pneumonia (VAP).We performed a prospective, randomized, double-blind, placebo-controlled trial of 146 mechanically ventilated patients at high risk of developing VAP. Patients were randomly assigned to receive enteral probiotics (n = 68) or an inert inulin-based placebo (n = 70) twice a day in addition to routine care.Patients treated with Lactobacillus were significantly less likely to develop microbiologically confirmed VAP compared with patients treated with placebo (40.0 vs. 19.1%; P = 0.007). Although patients treated with probiotics had significantly less Clostridium difficile-associated diarrhea than patients treated with placebo (18.6 vs. 5.8%; P = 0.02), the duration of diarrhea per episode was not different between groups (13.2 ± 7.4 vs. 9.8 ± 4.9 d; P = 0.39). Patients treated with probiotics had fewer days of antibiotics prescribed for VAP (8.6 ± 10.3 vs. 5.6 ± 7.8 d; P = 0.05) and for C. difficile-associated diarrhea (2.1 ± 4.8 SD d vs. 0.5 ± 2.3 d; P = 0.02). No adverse events related to probiotic administration were identified.These pilot data suggest that L. rhamnosus GG is safe and efficacious in preventing VAP in a select, high-risk ICU population. Clinical trial registered with www.clinicaltrials.gov (NCT00613795).
To treat or not to treat with corticosteroids radiation induced pneumonitis
Authors: Claudia Lucia Toma, Stefan Dumitrache-Rujinski, Ionela Belaconi, Diana Ligia Ionita, Roxana Nemes, Alina Croitoru, Miron Alexandru Bogdan
Journal: European Respiratory Journal (2013)

Aim – to assess the functional parameters evolution with and without corticotherapy in patients with radiation induced pneumonitis (RIP).  Material and methods – we evaluated 83 patients, 76 females (mean age 57.3 yrs), diagnosed with RIP after postoperative radiotherapy for thoracic cancers. History, physical exam, chest X-ray, and pulmonary function tests were obtained at diagnosis, after 3 months, and after one year.  Results – 47 patients (group A) had mild symptoms (fever, dyspnea, and cough) or asymptomatic and they didn’t receive any treatment, and 36 patients (group B) had moderate symptoms and received corticotherapy (prednisolone or prednisone 0.5 mg/kg/day with tapered doses) for 3 months. Both groups showed significant decrease of symptoms and decrease of the alveolar infiltrates/consolidation on chest-X ray after 3 months. There were no differences between groups in pulmonary volumes and flows (VC, FEV1, FEV1/VC ratio, TLC, RV) at baseline, after 3 months and one year. Group A showed an increase of the transfer factor (DLco), from 68.9% at 76.8% at 3 months and at 90.5% predicted at one year, and group B showed a raise in DLco from 61.1% at 68.5% at 3 months and at 69% predicted at one year. The difference between the two groups was non significant at baseline and after 3 months, but statistically significant after one year (p
SOME EFFECTS OF ENVIRONMENT ON EPIDERMAL DIFFERENTIATION. *
Authors: HONOR B. FELL
Journal: British Journal of Dermatology (1962)

Journal Article SOME EFFECTS OF ENVIRONMENT ON EPIDERMAL DIFFERENTIATION. Get access HONOR B. FELL, F.R.S. HONOR B. FELL, F.R.S. Strangeways Research Laboratory, Wort's Causeway, Cambridge Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 74, Issue 1, 1 January 1962, Pages 1–7, https://doi.org/10.1111/j.1365-2133.1962.tb13904.x Published: 01 January 1962
Endothelial Cell Pathway for Conduction of Hyperpolarization and Vasodilation Along Hamster Feed Artery
Authors: Geoffrey G. Emerson, Steven S. Segal
Journal: Circulation Research (2000)

Acetylcholine (ACh) evokes the conduction of vasodilation along resistance microvessels. However, it is not known which cell layer (endothelium or smooth muscle) serves as the conduction pathway. In isolated, cannulated feed arteries ( approximately 70 microm in diameter at 75 mm Hg; length approximately 4 mm) of the hamster retractor muscle, we tested the hypothesis that endothelial cells provide the pathway for conduction. Microiontophoresis of ACh (500 ms, 500 nA) onto the distal end of a feed artery evoked hyperpolarization (-13+/-2 mV) of both cell layers with vasodilation (15+/-1 microm) along the entire vessel. To selectively damage endothelial cells (confirmed by loss of vasodilation to ACh and labeling of disrupted cells with propidium iodide), an air bubble was perfused through a portion of the vessel lumen, or a 70-kDa fluorescein-conjugated dextran (FCD) was illuminated within a segment (300 microm) of the lumen. After endothelial cell damage, hyperpolarization and vasodilation conducted up to, but not through, the treated segment. To selectively damage smooth muscle cells (confirmed by loss of vasoconstriction to phenylephrine and labeling with propidium iodide), FCD was perifused around the vessel and illuminated. Vasodilation and hyperpolarization conducted past the disrupted smooth muscle cells without attenuation. We conclude that endothelial cells provide the pathway for conducting hyperpolarization and vasodilation along feed arteries in response to ACh.
Structural Correlates of Idiotopes
Authors: J M Davie, M V Seiden, N S Greenspan, C T Lutz, T L Bartholow, B L Clevinger
Journal: Annual Review of Immunology (1986)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Time–motion analysis and physiological data of elite under-19-year-old basketball players during competition
Authors: Nidhal Ben Abdelkrim, Saloua El Fazaa, Jalila El Ati
Journal: British Journal of Sports Medicine (2006)

The physical demands of modern basketball were assessed by investigating 38 elite under-19-year-old basketball players during competition. Computerised time–motion analyses were performed on 18 players of various positions. Heart rate was recorded continuously for all subjects. Blood was sampled before the start of each match, at half time and at full time to determine lactate concentration. Players spent 8.8% (1%), 5.3% (0.8%) and 2.1% (0.3%) of live time in high “specific movements”, sprinting and jumping, respectively. Centres spent significantly lower live time competing in high-intensity activities than guards (14.7% (1%) v 17.1% (1.2%); p&lt;0.01) and forwards (16.6% (0.8%); p&lt;0.05). The mean (SD) heart rate during total time was 171 (4) beats/min, with a significant difference (p&lt;0.01) between guards and centres. Mean (SD) plasma lactate concentration was 5.49 (1.24) mmol/l, with concentrations at half time (6.05 (1.27) mmol/l) being significantly (p&lt;0.001) higher than those at full time (4.94 (1.46) mmol/l). The changes to the rules of basketball have slightly increased the cardiac efforts involved during competition. The game intensity may differ according to the playing position, being greatest in guards.
Losartan attenuates bleomycin induced lung fibrosis by increasing prostaglandin E2 synthesis
Authors: M Molina-Molina
Journal: Thorax (2006)

<b>Background:</b> The angiotensin system has a role in the pathogenesis of pulmonary fibrosis. This study examines the antifibrotic effect of losartan, an angiotensin II type 1 receptor antagonist, in bleomycin induced lung fibrosis and its possible implication in the regulation of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) synthesis and cyclooxygenase-2 (COX-2) expression. <b>Methods:</b> Rats were given a single intratracheal instillation of bleomycin (2.5 U/kg). Losartan (50 mg/kg/day) was administrated orally starting one day before induction of lung fibrosis and continuing to the conclusion of each experiment. <b>Results:</b> Losartan reduced the inflammation induced by bleomycin, as indicated by lower myeloperoxidase activity and protein content in the bronchoalveolar lavage fluid. Collagen deposition induced by bleomycin was inhibited by losartan, as shown by a reduction in the hydroxyproline content and the amelioration of morphological changes. PGE<sub>2</sub> levels were lower in fibrotic lungs than in normal lungs. Losartan significantly increased PGE<sub>2</sub> levels at both 3 and 15 days. A reduction in COX-2 expression by bleomycin was seen at 3 days which was relieved by losartan. <b>Conclusions:</b> The antifibrotic effect of losartan appears to be mediated by its ability to stimulate the production of PGE<sub>2</sub>. Losartan, which is already widely used clinically, could be assessed as a new treatment in lung fibrosis.
Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies
Authors: Jean-Pierre J. Issa, Guillermo Garcia-Manero, Francis J. Giles, Rajan Mannari, Deborah Thomas, Stefan Faderl, Emel Bayar, John Lyons, Craig S. Rosenfeld, Jorge Cortes, Hagop M. Kantarjian
Journal: Blood (2003)
An Official American Thoracic Society Clinical Practice Guideline: The Diagnosis of Intensive Care Unit–acquired Weakness in Adults
Authors: Eddy Fan, Fern Cheek, Linda Chlan, Rik Gosselink, Nicholas Hart, Margaret S. Herridge, Ramona O. Hopkins, Catherine L. Hough, John P. Kress, Nicola Latronico, Marc Moss, Dale M. Needham, Mark M. Rich, Robert D. Stevens, Kevin C. Wilson, Chris Winkelman, Doug W. Zochodne, Naeem A. Ali
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Section:ChooseTop of pageAbstract <<ContentsOverviewIntroductionMethodsResultsDiscussionReferencesCITING ARTICLES
Alloantigen-specific idiotype-bearing receptors on mouse T lymphocytes. I. Specificity characterization and genetic association with the heavy-chain IgG allotype.
Authors: B Rubin, B Hertel-Wulff, A Kimura
Journal: The Journal of Experimental Medicine (1979)

The present study describes the qualitative reactions of a xenogeneic anti-idiotype (Id) antiserum produced in a mouse-gamma-globulin-tolerant rabbit (5,936) against B6 anti-CBA IgG antibodies. The results showed that such an anti-Id antiserum reacts specifically against anti-H-2k antibodies and against H-2k alloantigen-activated T cells from the following pairs of congenic mice: B10 (H-2b) and B10.D2 (H-2d); and A.BY (H-2b) and A.SW (H-2s), but not against C3H.SW (H-2b) and C3H.OH (H-2o); and BALB/b (H-2b) and BALB/c (H-2d). CB 20 (BALB/c mice with the Ig-1b allotype) anti-CBA T blasts also express idiotypic determinants that react with rabbit 5,936 antiserum. Thus, positive reactions are obtained between rabbit 5,936 anti-Id antiserum and anti-H-2k IgG preparations and T blasts from mice carrying the Ig-1b or Ig-1e allotype, but not from mice carrying the Ig-1a allotype. These reactions are qualitatively independent of the H-2 genotype of the Id-producing mice. Such a finding strongly suggests that the Id-bearing receptor molecules on mouse T cells are coded for by genes that are associated with the Ig heavy-chain-linkage group and not to the mouse histocompatibility complex. Furthermore, the anti-Id antibodies studied react preferentially against anti-H-2k antibodies or T cells with specificity toward the IAk-region-associated serological specificities. Thus, genes associated with the Ig heavy-chain-linkage group seem to be structural genes for at least T-cell receptors with specificity for IA-region-coded membrane antigens.
Variations in Lung Cancer Risk Among Smokers
Authors: Peter B. Bach, Michael W. Kattan, Mark D. Thornquist, Mark G. Kris, Ramsey C. Tate, Matt J. Barnett, Lillian J. Hsieh, Colin B. Begg
Journal: JNCI Journal of the National Cancer Institute (2003)

Although there is no proven benefit associated with screening for lung cancer, screening programs are attracting many individuals who perceive themselves to be at high risk due to smoking. We sought to determine whether the risk of lung cancer varies predictably among smokers.We used data on 18 172 subjects enrolled in the Carotene and Retinol Efficacy Trial (CARET)-a large, randomized trial of lung cancer prevention-to derive a lung cancer risk prediction model. Model inputs included the subject's age, sex, asbestos exposure history, and smoking history. We assessed the model's calibration by comparing predicted and observed rates of lung cancer across risk deciles and validated it by assessing the extent to which a model estimated on data from five CARET study sites could predict events in the sixth study site. We then applied the model to evaluate the risk of lung cancer among smokers enrolled in a study of lung cancer screening with computed tomography (CT).The model was internally valid and well calibrated. Ten-year lung cancer risk varied greatly among participants in the CT study, from 15% for a 68-year-old man who has smoked two packs per day for 50 years and continues to smoke, to 0.8% for a 51-year-old woman who smoked one pack per day for 28 years before quitting 9 years earlier. Even among the subset of CT study participants who would be eligible for a clinical trial of cancer prevention, risk varied greatly.The risk of lung cancer varies widely among smokers. Accurate risk prediction may help individuals who are contemplating voluntary screening to balance the potential benefits and risks. Risk prediction may also be useful for researchers designing clinical trials of lung cancer prevention.
A new method of disinfection of the flexible fibrebronchoscope.
Authors: A Garcia de Cabo, P L Martinez Larriba, J Checa Pinilla, F Guerra Sanz
Journal: Thorax (1978)

A modified method for rapid sterilisation of the fibrebronchoscope using immersion of the instrument in 0.1% benzalkonium chloride for five minutes followed by a further five minutes' immersion in 96% alcohol was tested both by deliberate contamination of rubber catheters and on bronchoscopes after use in patients. The method proved effective in eliminating a wide range of potentially pathogenic organisms.
Identification of Their Epitope Reveals the Structural Basis for the Mechanism of Action of the Immunosuppressive Antibodies Basiliximab and Daclizumab
Authors: Mascha Binder, Friederike-Nora Vögtle, Stefan Michelfelder, Fabian Müller, Gerald Illerhaus, Sangeeth Sundararajan, Roland Mertelsmann, Martin Trepel
Journal: Cancer Research (2007)

Abstract Interleukin-2 (IL-2) and its receptor (IL-2R) play a major role in cellular immunity. The monoclonal antibodies basiliximab and daclizumab directed against the IL-2R subunit CD25 are widely used to prevent graft or host rejection after allogeneic tissue transplantation. Although these antibodies have been used for this purpose for many years, their common epitope within the CD25 protein is unknown. We screened a random phage display library to isolate peptides specifically binding to basiliximab. A striking amino acid sequence motif was enriched. This motif is homologous to the peptide ERIYHFV comprising amino acid positions 116 to 122 within the extracellular domain of CD25, suggesting that this is the basiliximab epitope. Basiliximab and daclizumab binding of selected phage was specific, as no binding was observed to isotype antibody controls. Phage binding could be inhibited by the cognate peptide. In cells expressing mutant CD25, binding of basiliximab was abolished when two or more amino acids of the suspected epitope were changed. In contrast, basiliximab binding remained unaffected in cells expressing CD25 versions with mutations outside this epitope. We therefore conclude that the (116)ERIYHFV(122) string within CD25 is the epitope recognized by basiliximab and daclizumab. This epitope overlaps with the interaction site of CD25 and IL-2, thus revealing the structural basis for the inhibition of IL-2R binding by this class of immunosuppressive antibodies. [Cancer Res 2007;67(8):3518–23]