tbuckley/cabot-search huggingface dataset:
Oxidant-induced corticosteroid unresponsiveness in human bronchial epithelial cells
Authors: Irene Heijink, Antoon van Oosterhout, Nathalie Kliphuis, Marnix Jonker, Roland Hoffmann, Eef Telenga, Karin Klooster, Dirk-Jan Slebos, Nick ten Hacken, Dirkje Postma, Maarten van den Berge
Journal: Thorax (2013)

<h3>Background</h3> We hypothesised that increased oxidative stress, as present in the airways of asthma and chronic obstructive pulmonary disease (COPD) patients, induces epithelial damage and reduces epithelial responsiveness to suppressive effects of corticosteroids on proinflammatory cytokine production and barrier function. <h3>Methods</h3> We induced oxidative stress by H<sub>2</sub>O<sub>2</sub> and/or cigarette smoke extract (CSE) in human bronchial epithelial 16HBE cells and primary bronchial epithelial cells (PBEC) derived by brushings from asthma patients, COPD patients, and smoking and non-smoking control individuals. We investigated effects of budesonide on barrier function (electrical resistance) and TNF-α-induced proinflammatory cytokine production (IL-8/CXCL8, granulocyte macrophage-colony stimulating factor (GM-CSF)). <h3>Results</h3> We observed that H<sub>2</sub>O<sub>2</sub> and CSE reduce epithelial resistance. Budesonide significantly counteracted this effect, likely by protection against epidermal growth factor receptor-dependent cell-cell contact disruption. Furthermore, budesonide suppressed proinflammatory cytokine production. H<sub>2</sub>O<sub>2</sub> pretreatment reduced this effect of budesonide on cytokine production in both 16HBE cells and PBECs. Importantly, PBECs from asthma and COPD patients were less sensitive to budesonide with respect to cytokine production and barrier function than PBECs from control subjects. <h3>Conclusions</h3> Together, our data indicate that budesonide suppresses epithelial proinflammatory responses and barrier dysfunction and that oxidative stress reduces these effects in airway epithelium from asthma and COPD patients. Therefore, restoration of corticosteroid responsiveness in asthma and COPD may act to improve the airway epithelial barrier.
Role of immune recognition in latent allotype induction and clearance. Evidence for an allotypic network.
Authors: M L Yarmush, J A Sogn, P D Kern, T J Kindt
Journal: The Journal of Experimental Medicine (1981)

The role of allotype recognition in the regulation of the expression of latent allotypes has been investigated in two series of experiments. The first experiments were designed to investigate the apparent instability of latent allotypes in circulation. In these experiments, clearance rates of IgG preparations bearing allotypes matched and unmatched to the recipient were examined. In all cases, iodinated IgG matched in allotype to the recipient was cleared at a normal rate from the serum. However, in several cases, iodinated IgG of an unmatched allotype was cleared at a rate and in a manner suggesting prior sensitization of the recipient to IgG of that allotype. Such apparent sensitization correlated with the presence of the foreign allotypes as a latent allotype in several bleedings taken both before and after the clearance experiment. In the second series of experiments, designed to test the ability of antiallotype antibodies to affect the expression of latent allotypes, five rabbits were immunized first with purified antiallotype antibodies and then after 3-4 mo, with streptococcal vaccine. Examination of the antistreptococcal antibodies for latent allotype revealed, in all cases, that the allotype against which the antiallotype antibodies were directed was present in levels 8- to 20-fold greater than were observed before the antiallotype injections. These results indicate that recognition of allotypic determinants is an important element in the control of latent allotype expression and suggest the existence of a regulatory network involving antiallotype antibodies.
Different types of peroxisomes in human duodenal epithelium.
Authors: F Roels, M Espeel, M Pauwels, D De Craemer, H J Egberts, P van der Spek
Journal: Gut (1991)

Peroxisomes are ubiquitous organelles containing enzyme sequences for beta oxidation of fatty acids, synthesis of bile acids, and ether phospholipids. In the inherited peroxisomal diseases one or more enzymes are deficient in hepatic, renal, and fibroblast peroxisomes. We have examined peroxisomes by light and electron microscopy in 29 duodenal biopsy specimens (21 with normal mucosa) after staining for catalase activity, a marker enzyme. Peroxisomes were most numerous in the apices of the nucleus and at the villus base. Two types were distinguished: rounded to oval forms with a median lesser diameter of 0.23-0.31 microns, and tubular, vermiform organelles 0.1 microns thick and up to 3 microns long. Both types coexist in most patients. Tilting of sections and examination of semithin sections at 120 kV did not show connections between individual organelles. By morphometry, volume density was at least 0.45-0.62% of cellular volume, compared to 1.05% in human liver. In contrast, in four out of five individuals surface density of the peroxisomal membrane was 1.4-2.3 times higher than in control livers; this is expected to favour the exchange of metabolites. We suggest that intestinal peroxisomes contribute substantially to the breakdown of very long chain fatty acids.
Beclomethasone in steroid-dependent asthma. Effective therapy and recovery of hypothalamo-pituitary-adrenal function
Authors: D. R. Webb
Journal: JAMA (1977)

Beclomethasone dipropionate was administered by aerosol to 30 patients whose chronic bronchial asthma required oral corticosteroid therapy. During the initial 12 weeks of the trial, beclomethasone therapy could be discontinued in 12 of 16 patients in contrast to only one of 14 patients receiving the inert aerosol placebo. Patients receiving the placebo were then given beclomethasone, and prednisone therapy was discontinued in five more. During six months of observation, adrenal function improved and steroid toxic reactions decreased in patients in whom oral corticosteroid therapy had been discontinued. Beclomethasone aerosol was generally well-tolerated. Asymptomatic thrush developed in four patients and rhinitis developed in ten patients as prednisone therapy was discontinued.
Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy
Authors: Sanjeev Shangary, Shaomeng Wang
Journal: The Annual Review of Pharmacology and Toxicology (2008)

Tumor suppressor p53 is an attractive cancer therapeutic target because it can be functionally activated to eradicate tumors. Direct gene alterations in p53 or interaction between p53 and MDM2 proteins are two alternative mechanisms for the inactivation of p53 function. Designing small molecules to block the MDM2-p53 interaction and reactivate the p53 function is a promising therapeutic strategy for the treatment of cancers retaining wild-type p53. This review will highlight recent advances in the design and development of small-molecule inhibitors of the MDM2-p53 interaction as new cancer therapies. A number of these small-molecule inhibitors, such as analogs of MI-219 and Nutlin-3, have progressed to advanced preclinical development or early phase clinical trials.
Ineffective Perfusion-Contraction Matching in Conscious, Chronically Instrumented Pigs With an Extended Period of Coronary Stenosis
Authors: Raymond K. Kudej, Bijan Ghaleh, Naoki Sato, You-Tang Shen, Sanford P. Bishop, Stephen F. Vatner
Journal: Circulation Research (1998)

Several models purported to represent hibernating myocardium involve a coronary stenosis (CS) to reduce blood flow (BF) and function without eliciting necrosis in anesthetized pigs. The goal of the present study was to determine whether sustained moderate reduction in coronary BF in conscious pigs induced hibernating myocardium, ie, perfusion-contraction matching with no necrosis. These experiments were conducted in conscious pigs chronically instrumented with a coronary artery BF probe and hydraulic occluder, left ventricular (LV) pressure gauge, and wall thickening (WT) crystals in the potentially ischemic and nonischemic zones. The hydraulic occluder was inflated to induce a stable 41+/-4% reduction in BF for 24 hours. Ischemic zone systolic WT fell initially with CS and then continued to decline during the period of CS even though blood flow did not change further, suggesting the induction of myocardial stunning. At 2 days after release of CS, WT was still depressed by 48+/-15%. Assessment of necrosis by histology or triphenyltetrazolium chloride showed 40+/-5% multifocal patchy necrosis interspersed with normal tissue involving the inner one third to one half of the ventricular wall. Regional myocardial BF (radioactive microsphere technique) was assessed by dividing the entire LV into an average of 488+/-59 pieces and examining the spatial distribution of BF within the area at risk (AAR). BF in the samples in the area of patchy necrosis was reduced (-66+/-4% from a baseline of 1.55+/-0.27 mL x min(-1) x g(-1)), whereas BF was maintained in samples in the AAR without necrosis (-2+/-7% from a baseline of 1.25+/-0.22 mL x min(-1) x g(-1)). These findings indicate that when hypoperfusion induced by CS in conscious pigs is sustained, the result is necrosis rather than hibernating myocardium. The remainder of the AAR, which lacked necrosis, might have been mistaken for hibernating myocardium had only histology been evaluated and BF not been measured and found to be at normal levels.
Generation of national political priority for surgery: a qualitative case study of three low-income and middle-income countries
Authors: Anna J Dare, Josh Bleicher, Katherine C Lee, Alex E Elobu, Thaim B Kamara, Osborne Liko, Samuel Luboga, Akule Danlop, Gabriel Kune, Lars Hagander, Andrew J M Leather, Gavin Yamey
Journal: The Lancet (2015)
Effect of Radiation and Ibuprofen on Normoxic Renal Carcinoma Cells Overexpressing Hypoxia-Inducible Factors by Loss of von Hippel–Lindau Tumor Suppressor Gene Function
Authors: Sanjeewani T. Palayoor, Melissa A. Burgos, Azadeh Shoaibi, Philip J. Tofilon, C. Norman Coleman
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Tumor hypoxia is a major limiting factor for radiation therapy. Hypoxia-inducible factors (HIFs) are overexpressed in several human cancers and are considered prognostic markers and potential targets for cancer therapy. The purpose of the present study was to investigate the impact of HIFs on radiosensitivity. Experimental Design: Renal clear cell carcinoma (RCC) cell lines overexpressing HIFs under normoxic conditions because of inactivation of von Hippel–Lindau tumor suppressor gene function (VHL-ve) and their matched pairs in which overexpression of HIFs was abolished by expression of functional VHL (VHL+ve) were irradiated. Radiosensitivity was determined by clonogenic assay. HIF and VHL protein levels were evaluated by Western blot analysis. RCC cells were also treated with ibuprofen, a radiosensitizer and HIF inhibitor in prostate cancer cells. The effect of ibuprofen on radiosensitization and HIF and VHL proteins was compared in RCC matched-pair cell lines. Results: The data showed only small differences in the radiosensitivity between the cells overexpressing HIFs and cells with basal HIF levels. The dose-modifying factors for C2, 786-0, and A498 RCC cells were 1.14, 1.14 and 1.15, respectively. Radiation did not alter HIF or VHL protein levels. Ibuprofen inhibited HIFs in VHL+ve cells expressing basal levels of HIFs. In VHL-ve cells overexpressing HIFs, the inhibition was very modest. Ibuprofen radiosensitized C2 RCC cells to the same extent irrespective of their HIF status. Conclusions: Overexpression of HIFs in RCC cells harboring VHL mutations has only a modest effect on the radiosensitivity. Radiosensitization by ibuprofen appears to be independent of HIF status.
The Invs Gene Encodes a Microtubule-Associated Protein
Authors: Jens Nürnberger, Andreas Kribben, Anabelle Opazo Saez, Gerd Heusch, Thomas Philipp, Carrie L. Phillips
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Microtubule networks are important for many vital processes such as mitosis, cell polarity, and differentiation. Ciliary architecture and function closely depend on the microtubule cytoskeleton, and recent studies suggest a role of apical cilia of renal epithelia in the pathogenesis of polycystic kidney disease. This study evaluates the localization, potential interacting partners, and functional aspects of the Invs gene product inversin. Only recently, INVS has been identified as the gene that is mutated in nephronophthisis type 2, an autosomal recessive polycystic kidney disease. Using immunoprecipitation and co-pelleting assays, we show that the Invs gene product inversin forms a stable complex with tubulin in cultured renal epithelial cells. Inversin localizes to several components of the cytoskeleton including ciliary, random, and polarized microtubule pools. During cell divison, inversin is recruited to mitotic spindle fibers. After microtubule depolymerization using colcemid inversin and tubulin staining is no longer characterized by a network pattern but by homogeneous, diffuse distribution. Inversin does not coprecipitate with tubulin after addition of colcemid. After removal of colcemid, inversin immunofluorescence reappears together with tubulin in centrioles. Treatment with the microtubule stabilizing agent paclitaxel leads to severe alteration of the microtubule cytoskeleton with bundling and formation of long spindles of tubulin and inversin. In conclusion, inversin is closely associated with the microtubule cytoskeleton, and its spatial distribution is dependent on tubulin polymerization. Hence, altered inversin-tubulin interaction may impair ciliary function and thereby contribute to cyst development in nephronophthisis.
So, are we the massively lucky species?
Authors: Derek C. Penn, Keith J. Holyoak, Daniel J. Povinelli
Journal: Behavioral and Brain Sciences (2012)

Abstract We are in vehement agreement with most of Vaesen's key claims. But Vaesen fails to consider or rebut the possibility that there are deep causal dependencies among the various cognitive traits he identifies as uniquely human. We argue that “higher-order relational reasoning” is one such linchpin trait in the evolution of human tool use, social intelligence, language, and culture.
Anti–Vascular Endothelial Growth Factor Therapies as a Novel Therapeutic Approach to Treating Neurofibromatosis-Related Tumors
Authors: Hon Kit Wong, Johanna Lahdenranta, Walid S. Kamoun, Annie W. Chan, Andrea I. McClatchey, Scott R. Plotkin, Rakesh K. Jain, Emmanuelle di Tomaso
Journal: Cancer Research (2010)

Abstract Patients with bilateral vestibular schwannomas associated with neurofibromatosis type 2 (NF2) experience significant morbidity such as complete hearing loss. We have recently shown that treatment with bevacizumab provided tumor stabilization and hearing recovery in a subset of NF2 patients with progressive disease. In the current study, we used two animal models to identify the mechanism of action of anti–vascular endothelial growth factor (VEGF) therapy in schwannomas. The human HEI193 and murine Nf2−/− cell lines were implanted between the pia and arachnoid meninges as well as in the sciatic nerve to mimic central and peripheral schwannomas. Mice were treated with bevacizumab (10 mg/kg/wk i.v.) or vandetanib (50 mg/kg/d orally) to block the VEGF pathway. Using intravital and confocal microscopy, together with whole-body imaging, we measured tumor growth delay, survival rate, as well as blood vessel structure and function at regular intervals. In both models, tumor vessel diameter, length/surface area density, and permeability were significantly reduced after treatment. After 2 weeks of treatment, necrosis in HEI193 tumors and apoptosis in Nf2−/− tumors were significantly increased, and the tumor growth rate decreased by an average of 50%. The survival of mice bearing intracranial schwannomas was extended by at least 50%. This study shows that anti-VEGF therapy normalizes the vasculature of schwannoma xenografts in nude mice and successfully controls the tumor growth, probably by reestablishing a natural balance between VEGF and semaphorin 3 signaling. Cancer Res; 70(9); 3483–93. ©2010 AACR.
AEROBIC FITNESS, BONE HEALTH, HYDRATION AND EXERTION DURING RACING IN PROFESSIONAL JOCKEYS IN HONG KONG
Authors: SH Wong, J O'Reilly
Journal: British Journal of Sports Medicine (2013)

Jockeys often make weight by methods such as caloric restriction and voluntary dehydration, which may lead to a compromise in muscle and liver glycogen stores and blood glucose concentration, all of which are necessary for optimal racing performance. However, little information is known about the physiological measures of the Hong Kong jockeys. Therefore, the purpose of this study was to examine aerobic fitness and bone health of Hong Kong professional jockeys and their hydration status on race day morning, as well as their work intensity during competitive races. 15 professional jockeys in Hong Kong took part in the study. Maximal aerobic capacity (VO 2max ) and bone mineral densities of each wrist and calcaneus were assessed in the laboratory. On race-day, the first morning urine sample was assessed for urine specific gravity (USG) and each jockey wore a heart rate monitor from 45 min prior to their first race until 15 min after their final race of the day. VO 2max for the group was 57±5 ml.kg.h −1 . Mean combined T-scores and Z-scores for bone density were −1.04±1.19 and −0.74±1.10 respectively. USG was 1.0256±0.0058 g.mL −1 . Mean heart rate during racing was 165±5 bpm. VO 2max of Hong Kong jockeys was higher than that previously found in their UK counterparts. However, the jockeys had a markedly lower bone mineral density than would be expected for their age (Palmer et al . MSSE 2003;35:20) leaving them at a greater susceptibility to fracture from an impact that might otherwise leave them unharmed (Brown and Josse. Can Med Assoc J 2002;167:1–34). The jockeys were considerably dehydrated in an attempt to make weight for racing. Heart rate data indicated that the jockeys performed regular bouts of high-intensity exercise during the race day. A review of dietary, physical activity and hydration practices is recommended for this athletic group.
Four Series of Cases of Sewer-Gas Poisoning
Authors: W. G. Nash
Journal: BMJ (1899)

THE various diseases of a septic nature which may be pro- duced by sewer-gas poisoning are well exemplified by four series of cases which have occurred in my practice during the last seven years.FIRST SERIES.In December, I89I, a ladywas confined and attended by Mr. Kinsey at Bedford.Tile labour was quite normal, but was followed by pelvic cellulitis.When I joined Mr. Kinsey at the end of January, I892, there was a large mass in the left iliac region of this patient.This gradually disappeared during the next two months, and the patient entirely recovered.Between the end of January, 1892, and August of the same year, there occurred in this house the following cases: Acute rlleumatism ... 2 cases.Diphtlheria ... i case.
Clinical Lecture on the Contagiousness of Pulmonary Consumption
Authors: I. B. Yeo
Journal: BMJ (1882)

GENTLEMEN,-Within the last few weeks, you have had an opportunity of seeing, in the Physiological Laboratory of King's College, specimens of certain micro-organisms, prepared by Koch of Berlin, and described by him as the bacillus of tubercle.*This organism is believed by him to be the active agent in the origin and spread of tuberculous diseases.You have also had an opportunity of seeing that this micro-organism can be artificially cultivated and successive generations produced, each retaining with undiminished virulence the power of producing tubercle when introduced into the bodies of certain animals.Now, this demonstration, which you have seen with your own eyes, introduces you to problems in pathology and in practical medicine, the importance of which it is impossible to exaggerate.Never, in the whole of the past history of medical science and of medical discovery, have propositions been advanced of greater import than those which have been advanced and maintained in connection with this discovery.Let me state to you, in language as clear and simple as I can, what these propositions are.I. Tubercle is an infective malady, originating in a specific virus, and propagated by the conveyance of that virus from body to body, and originating in no other way.2. The specific virus of tubercle consists of a particular micro- organism, found only in tubercle ; this organism can be seen in the cells of tubercle, can be obtained in a separate form, and cultivated in successive generations, without losing its original properties.3. Certain forms of disease, termed "scrofulous", are essentially tuberculous; and their characteristic anatomical morbid products con- tain the infective organism peculiar to tubercle.4. The disease known as pulminonary consumption is, in the main, a tuberculous disease, and is depend'ent on the presence and propagation in the body of the infective organism characteristic of tubercle.5. Pulmonary consumption is a-contagious malady.Of these five propositions, it is claimed for the three first that they rest on demonstration, as I propose to show you; the last two are, more or less, of the nature of inferences from the three preceding; and, in connection with these, we may expect to'find there will exist some differences of opinion.The idea, that consumption is a contagious disease, is not a new one.It is a doctrine which has always been maintained in -the south of Europe-in Italy, Spain, and Portugal.Galen believed it, Morgagni believed it, and great names in the history of medicine, from their time to ours, may be found both for arxd against it.
Endobronchial hamartoma removed by rigid bronchoscope
Authors: AA Sahin, A Aydiner, F Kalyoncu, L Tokgozoglu, YI Baris
Journal: European Respiratory Journal (1989)

An endobronchial hamartoma of the right lower lobe was discovered in a 60 yr old female patient. She had been diagnosed and treated for chronic intractable bronchial asthma for more than 10 yrs. The endobronchial hamartoma was successfully removed with a rigid bronchoscope.
Extracorporeal Removal of Drugs and Poisons by Hemodialysis and Hemoperfusion
Authors: R E Cutler, S C Forland, P G S Hammond, J R Evans
Journal: The Annual Review of Pharmacology and Toxicology (1987)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More