tbuckley/cabot-search huggingface dataset:
Fiberoptic bronchoscopy in brain-dead organ donors.
Authors: B Riou, R Guesde, Y Jacquens, R Duranteau, P Viars
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Criteria for selecting lung donors include normal chest X-ray and adequate gas exchange, but normal bronchoscopy is not always required. Thus, we conducted a prospective study of fiberoptic bronchoscopy in 72 brain-dead donors scheduled for multiple organ procurement. Chest X-ray was considered normal in 37 donors (51%), and PaO2 was > 400 mm Hg with an FIO2 of 100% in 34 donors (47%). Fiberoptic bronchoscopy was normal in only 24 donors (33%). In the remaining 48 donors, inhalation of gastric contents (n = 26) or blood (n = 17), pulmonary contusion (n = 5), or purulent bronchial secretions (n = 4) were noted. In the 26 donors with normal chest X-ray and PaO2 > 400 mm Hg with FIO2 of 100%, bronchoscopy was abnormal in 10 donors (38%). In 33 donors, arteriovenous difference in oxygen content (2.4 +/- 0.8 ml O2/100 ml), and pulmonary shunt (0.30 +/- 0.11, range 0.13-0.49) were measured. In the 15 donors with PaO2 > 400 mm Hg, pulmonary shunt was 0.23 +/- 0.07 (range 0.13-0.35). Our study suggests that chest X-ray and arterial blood gas analysis are not sufficient, and that fiberoptic bronchoscopy should be routinely performed to select potential lung donors. Even in brain-dead donors, only the measurement of pulmonary shunt can precisely assess pulmonary gas exchange.
Sesame seed and sesame seed oil contain masked allergens of growing importance
Authors: G. Kanny, C. Hauteclocque, D. A. Moneret-Vautrin
Journal: Allergy (1996)

Sesame seed and sesame seed oil have been thought of as rare causes of food allergy, representing less than 1% of all food allergy cases. We now report nine cases of IgE-dependent allergy to sesame seed and/or sesame seed oil, six of which were diagnosed in 1995 alone. Our skin test results draw attention to the poor quality of a commercial sesame seed extract and the good sensitivity of skin prick tests made with a freshly prepared sesame seed flour extract. The diagnosis of this food allergy was established by double-blind oral provocation tests, with doses of sesame seed flour ranging from 100 mg to 10 g. Allergy to sesame seed oil was also demonstrated in some cases. The sensitivity of the Pharmacia Phadebas CAP System for the detection of sesame seed-specific IgE was only mediocre. We draw attention to the important use of sesame seed in modern cooking, a fact which may explain the growing frequency of this allergy. We underline the particular risk with sesame seed oil. Sesame seed should also be considered a cause of allergic reactions to drug products and cosmetics.
Oxygen radicals: mediators of gastrointestinal pathophysiology.
Authors: D A Parks
Journal: Gut (1989)

Oxygen radicals: mediators of gastrointestinal pathophysiologyRecent evidence suggests that reactive oxygen metabolites are mediators of the microvascular and parenchymal cell injury associated with ischaemia and subsequent reperfusion.Under normal conditions, approximately 95% of molecular oxygen in biological systems undergoes controlled reduction through the addition of four electrons (tetravalent) in the mitochondrial cytochrome oxidase system to form water. ' The remaining molecular oxygen undergoes sequential, univalent reduction to produce the partially reduced oxygen free radical intermediates, superoxide anion (02-), hydrogen peroxide (H202) and the highly reactive hydroxyl radical (OH).Nature has provided a myriad of antioxidant enzymes and scavengers to protect against the deleterious effects of these highly reactive metabolites of oxygen.The primary defence against oxidative insults to the tissue include the enzymes, superoxide dismutase, catalase, and glutathione peroxidase.Superoxide dismutases are a family of predominantly intracellular metallo- proteins that catalyse dismutation of 02to H202.Only trace amounts of superoxide dismutase activity are detected in extracellular fluid -that is, plasma, spinal fluid and lymph.2Two enzyme systems are important in regulating the intracellular concentration of H202.Catalase is a haemo- protein which catalyses decomposition of H202 to water.Glutathione peroxidase is a cytoplasmic, selenium containing enzyme which catalyses decomposition of H202 or organic peroxides to water or the corresponding organic alcohol.The antioxidant activity of glutathione peroxidase is coupled to the oxidation of reduced glutathione to oxidised glutathione which can be subsequently reduced by glutathione reductase using NADPH as the reducing agent.A selenium independent form of glutathione peroxidase has recently been described.'In addition to antioxidant enzymes, a multitude of water soluble -for example, ascorbic acid, cysteine, and lipid solublefor example, a-tocopherol, ,6-carotene, antioxidants provide a second line of defence against oxidant induced tissue injury. Sources of oxygen radicalsOxygen free radicals may be formed from several sources, including: components of the mitochondrial electron transport system; endoplasmic reticulum; prostaglandin synthetase and lipoxygenase systems; soluble enzymes and proteins; and autoxidation of several compounds and xeno- biotics.Of the multitude of potential sources of reactive oxygen metabolites, two major enzymes have been implicated in the tissue damage associated with ischaemia reperfusion, xanthine oxidase, and neutrophilic NADPH oxidase.
Résultats d'une enquête régionale de pratique sur l'indication de la coloscopie et la surveillance des sujets à risque élevé de cancer colorectal
Authors: A Michaud-Herbst, V Jouhet, P Ingrand, JC Letard, JP Dupuychaffray, T Barrioz, M Beauchant
Journal: Endoscopy (2010)

Introduction: Dans le cadre d'une enquête régionale, nous avons évalué la pratique des gastroentérologues des établissements publics et privés concernant lesindications de la coloscopie par rapport aux recommandations de l'ANAES.
Adaptive misbelief or judicious pragmatic acceptance?
Authors: Keith Frankish
Journal: Behavioral and Brain Sciences (2009)

Abstract This commentary highlights the distinction between belief and pragmatic acceptance, and asks whether the positive illusions discussed in section 13 of the target article may be judicious pragmatic acceptances rather than adaptive misbeliefs. I discuss the characteristics of pragmatic acceptance and make suggestions about how to determine whether positive illusions are attitudes of this type.
Rook/Wilkinson/Ebling Textbook of Dermatology, vols 1-4
Authors: Brian Cook
Journal: JAMA (1994)

The fifth edition of Rook's<i>Textbook of Dermatology</i>has maintained the encyclopedic breadth and readability that warrant its reputation as the finest dermatology reference text available. The fifth edition has expanded to more than 3500 pages and 1767 illustrations filling four volumes. The 53 contributors enhance the readability of this work by adhering to a uniform template of etiology, pathology, clinical features, and treatment, including definition, incidence, prevalence, course and prognosis, differential diagnosis, and associated findings. The text is designed to be used as a reference and benefits from its uniform style, which avoids the needless duplication and verbosity all too common in multiauthored reference works. It is a herculean task to read this excellent text cover to cover, although the intrepid dermatologist in training would be well served by the exercise and surprised by the work's readability. The addition of bold type in the index to highlight the primary
41 S-Collate COHORT ‘REAL-LIFE’ STUDY: EFFICACY AND SAFETY OF PEGINTERFERON alfa-2a (40KD) IN 1233 PATIENTS WITH CHRONIC HEPATITIS B ACCORDING TO ASIAN AND CAUCASIAN RACE
Authors: P. Marcellin, Q. Xie, T. Piratvisuth, G.R. Foster, R. Flisiak, X.Y. Chen, Y. Xie, Y.P. Chen, S.W. Paik, D. Messinger, L. Regep, H. Wedemeyer
Journal: Journal of Hepatology (2013)
Vasectomy and Increased Risk of Prostate Cancer-Reply
Authors: Edward Giovannucci, Alberto Ascherio, Eric B. Rimm, Graham A. Colditz, Meir J. Stampfer, Walter C. Willett
Journal: JAMA (1993)

In Reply.  —We compared our results of the health professionals with SEER rates as suggested by Sidney et al and found ratios to SEER rates similar to those observed in Kaiser (aged 60 to 64 years, health professionals/SEER rate, 0.84 vs Kaiser/SEER rate, 0.89; aged 65 to 69 years, 0.79 vs 0.91, respectively; aged 70 to 74 years, 0.77 vs 0.77, respectively; and aged 75 to 79 years, 1.00 vs 1.18, respectively). The comparison suggested by Morgentaler and DeWolf does not account for age differences. Further, the prostate-specific antigen test was not widely used for screening when we conducted the studies and, thus, unlikely to have caused bias. The men with and without vasectomy had similar screening histories,1including frequency of rectal examination, which was the primary screening technique for prostate cancer during the study's time period.  Dr Levine suggests that because of a first encounter with a urologist,
Abstract 795: Epigenetics, cell cycle and drug-resistant ovarian cancer
Authors: Nur Arnida Mohammed Safuwan, Pritlata Chivers, Tim Crook, Nelofer Syed, Helen M. Coley
Journal: Cancer Research (2012)

Abstract Epithelial ovarian cancer (EOC) is the most lethal of the gynaecological malignancies and currently stage III/IV disease is associated with a 25% 5 year survival rate. A major factor associated with advanced EOC is the development of drug resistant disease, characterised by a lack of response to platinum and taxane based agents. In an effort to clarify mechanisms underlying chemorefractory EOC we have developed a number of drug resistant cancer cell lines. DNA microarray screening of drug resistant versus drug sensitive cell lines (combining a methylation reversal step using demethylating agents) indicated down-regulation of a number of genes with evidence of epigenetic silencing by promoter methylation in many cases. We have identified P57kip2 a cyclin dependent kinase inhibitor (CDKi) as a gene that is subjected to methylation in carboplatin-resistance, as shown in the PEO1CarbR line. Using a siRNA approach, silencing of the p57kip2 gene in drug sensitive parental PEO1 or SKOV-3 cells gave rise to a reduced sensitivity to platinum agents i.e. cisplatin or carboplatin as assessed using apoptosis with the annexinV assay and flow cytometry. Using chemosensitivity testing (MTT) of PEO1 parental and PEO1CarbR lines versus seliciclib (a CDK2 inhibitory drug) we saw an association with sensitivity to this agent with down-regulation of p57kip2. The IC50 values obtained for the human ovarian cancer cell line PEO1 and PEO1CarboR were 27.4 and 19.2μM, respectively (p = &amp;lt;0.05). Cell cycle analysis of seliciclib treated cells indicated a prolonged S-phase as a marker of increased sensitivity to the drug and an increased apoptotic response in p57kip2 silenced cells. Our data suggest that CDK inhibitors such as seliciclib may have utility in tumours that show downregulation of the endogenous CDKi p57kip2 and identification of such patients may indicate a sub-group that respond preferentially to seliciclib. The same screening platform also enabled us to identify wee1 and stratifin (14-3-3α) as genes significantly downregulated in taxane-resistant cell lines. The 2 gene products are important in maintaining genomic stability alongside other proteins such as Chk1 and ATR. Wee1 controls G2M by keeping CDK2/Cyclin B inactive whilst binding of 14-3-3 isoforms enhances its activity. Demethylation treatment using 5′aza-cytidine and Trichostatin A unmasked gene expression, indicating that these genes are hypermethylated in taxane-resistant cell line. Current work aims to confirm further the role of these 2 genes in drug resistance by a series of knock-in and knock-out experiments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 795. doi:1538-7445.AM2012-795
Immunotherapy for cancer
Authors: A. E Johnson
Journal: Journal of the Royal Society of Medicine (2002)

Dr Grange and colleagues conclude that recent advances in the understanding of the nature of the immune response will enable a move ‘from the empirical to the rational approach’ in devising immunotherapy for cancer (June 2002 JRSM1). They quote latent periods in the progress of cancer and of tuberculosis as evidence that an immune response is involved in both cases. This need not be so.

In both diseases there is cell death in the centre of masses (whether tubercles or cancers) that have outstripped their circulation2. In cancers the dead tissue may become organized and potentially proliferative cells sequestered, remote from blood-borne treatment and resistant to radiation through hypoxia. Successful treatment of the outer well-vascularized tumour leaves a core that may be slowly resorbed until the sequestered cells are exposed to a fresh blood supply; regrowth then occurs.

In the interpretation of so-called latent periods in cancer the most influential factor is a huge range of growth rates. In our series of unselected breast cancers3 the 95% confidence intervals of the distribution of inferred volume doubling times were 6 and 121 days. Some 30 doublings of volume from a single cell are required to produce a clinically detectable tumour of about 1 cm in diameter. Thus growth from a single cell might take more than 10 years to achieve a diagnosable size. The published work abounds with much more slowly growing examples4. After treatments, any residual subclinical disease is unmeasurable over a range of sizes that represent three-quarters of the life-span of a tumour.

One may not assume that apparent delays in growth result from an immune response.
Epithelial stem cell mutations that promote squamous cell carcinoma metastasis
Authors: Ruth A. White, Jill M. Neiman, Anand Reddi, Gangwen Han, Stanca Birlea, Doyel Mitra, Laikuan Dionne, Pam Fernandez, Kazutoshi Murao, Li Bian, Stephen B. Keysar, Nathaniel B. Goldstein, Ningjing Song, Sophia Bornstein, Zheyi Han, Xian Lu, Joshua Wisell, Fulun Li, John Song, Shi-Long Lu, Antonio Jimeno, Dennis R. Roop, Xiao-Jing Wang
Journal: Journal of Clinical Investigation (2013)

Squamous cell carcinomas (SCCs) originate in stratified epithelia, with a small subset becoming metastatic. Epithelial stem cells are targets for driver mutations that give rise to SCCs, but it is unknown whether they contribute to oncogenic multipotency and metastasis. We developed a mouse model of SCC by targeting two frequent genetic mutations in human SCCs, oncogene Kras(G12D) activation and Smad4 deletion, to mouse keratin 15-expressing (K15+) stem cells. We show that transgenic mice developed multilineage tumors, including metastatic SCCs. Among cancer stem cell-enriched (CSC-enriched) populations, those with increased side population (SP) cells correlated with epithelial-mesenchymal transition (EMT) and lung metastasis. We show that microRNA-9 (miR-9) contributed to SP expansion and metastasis, and miR-9 inhibition reduced the number of SP cells and metastasis. Increased miR-9 was detected in metastatic human primary SCCs and SCC metastases, and miR-9-transduced human SCC cells exhibited increased invasion. We identified α-catenin as a predominant miR-9 target. Increased miR-9 in human SCC metastases correlated with α-catenin loss but not E-cadherin loss. Our results demonstrate that stem cells with Kras(G12D) activation and Smad4 depletion can produce tumors that are multipotent and susceptible to EMT and metastasis. Additionally, tumor initiation and metastatic properties of CSCs can be uncoupled, with miR-9 regulating the expansion of metastatic CSCs.
Set menus and clinical freedom.
Authors: P Kinnersley, P Owen, C Wilkinson, J Richards
Journal: BMJ (1991)

for our patients in renal failure should not be greater than our concern for other human beings, even if we are nephrologists or transplant surgeons.Giving a fair price is not the solution for poverty.This is a worldwide problem.Opening such a door will add to the miseries ofThird World countries as they would become the sole source of organs for sale.
Abstract 2342: Identification of oncogenes and tumor suppressor genes using immortalized lung bronchial epithelial cells and small airway epithelial cells
Authors: Boning Gao, Chunxian Huang, Luc Girard, Adi F. Gazdar, Jerry W. Shay, John D. Minna
Journal: Cancer Research (2012)

Abstract We have immortalized human normal proximal bronchial epithelial cells (HBECs) for the study of lung tumors arising in the central compartment of the lung, and now have over 30 of these strains (growing in defined KSFM media) including many isogenic derivatives with various oncogenic changes (Can Res 2004, Can Res 2006). We have extended this by immortalizing normal distal (small airway) epithelial cells that serve as models for the study of tumors arising in the peripheral compartment of the lung. Using Cdk4 and hTERT exogenous expression vectors (as used for HBECs) and serum free defined media, we have immortalized (N= 19) human small airway epithelial cells (HSAECs) from peripheral lung. We have characterized the HBECs and HSAECs and found they have the property of lung basal /stem cells. In the current study, we compared the genome-wide RNA expression profile of HBECs/ HSAECs with 108 lung tumor cell lines and identified a panel of genes that are differentially expressed in these two cell types. We found ∼ 1200 genes that are 2 fold over expressed in tumor cells lines compared with HBECs/HSAECs (p ≤ 0.005). Many known lung tumor oncogenes such as members in cancer/testis (CT) antigen families (XAGE/GAGE/MAGE), proliferation-promoting E2F2 transcription factors, and Kinesin family are over-expressed in tumor lines validating the comparison strategies. In addition, we found genes that had been shown to be involved in other types of tumors but had not been reported in lung tumors. Importantly, we found several genes that had not been implicated as oncogenes previously, thus these are potential novel oncogenes for lung tumor transformation. We also found ∼1300 genes that are 2 fold over expressed in HBECs/HSAECs compared with tumor cell lines (p≤ 0.006). Many of the genes are lung basal cell markers (Keratin and Laminin family members) or known tumor suppressor genes (p53 binding genes and metallothionein genes) as expected. Like in the case of tumor specific genes, we found several genes that had not been reported functioning in the inhibition of tumor transformation. Thus, these are candidate tumor suppressor genes. The current study showed that the immortalized HBEC and HSAECs are ideal models for the discovery of novel oncogenes and tumor suppressor genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2342. doi:1538-7445.AM2012-2342
P1112 LONG TERM FOLLOW-UP OF PATIENTS TREATED WITH SOFOSBUVIR IN THE FISSION, POSITRON, FUSION AND NEUTRINO PHASE 3 STUDIES
Authors: W. Cheng, S. Shafran, K. Beavers, H. Mo, J. McNally, D.M. Brainard, W.T. Symonds, M. Chojkier, A. Mangia, C. Schwabe
Journal: Journal of Hepatology (2014)
Mucus glycoprotein biosynthesis in the human gall bladder: inhibition by aspirin.
Authors: M Rhodes, A Allen, T W Lennard
Journal: Gut (1992)

Aspirin, which inhibits mucin secretion in the gastrointestinal tract prevents gall stone formation in animals and may reduce gall stone recurrence in man. This study examines the effect of aspirin on mucin synthesis in human gall bladder explants. Two hundred explants were cultured with 3H-glucosamine (74 kBq/ml) for 24 hours at 37 degrees C. Mucin and other glycoproteins were isolated by papain digestion (72 hours) and exhaustive dialysis (144 hours) to remove non-incorporated radioactivity and digested protein. 3H-glucosamine was readily incorporated into glycoprotein. Pooled gall bladder explants were fractionated on a CsCl density gradient and by gel filtration on Sepharose 2B and 4B to confirm that >90% radioactivity was incorporated into mucin. Acetylsalicylic acid (230-666 micrograms/ml) significantly reduced total 3H-glucosamine incorporation (43-89%), p<0.01 (unpaired t test). Diclofenac (125-1250 micrograms/ml), similarly reduced incorporation by 45-97% p<0.001 (unpaired t test). Inhibition of mucin glycoprotein biosynthesis was irreversible with both drugs. Analysis of pooled samples on Sepharose 4B showed abolition of radioactive incorporation into mucin but no effect on incorporation into low molecular weight glycoprotein material (10% of total incorporation). This study provides a method for measuring human gall bladder mucin synthesis and shows its irreversible inhibition by acetylsalicylic acid and diclofenac at concentrations compatible with a therapeutic dose.
Genetics and Diabetic Renal Disease
Authors: Carl Erik Mogensen
Journal: Diabetes Care (2003)

Diabetic renal disease is still an extremely important and common complication in both type 1 and type 2 diabetic patients. Every clinician and nephrologist knows that diabetic patients constitute a large proportion of clientele in the dialysis unit, perhaps ∼50% or more, particularly in the U.S. and Japan. The figure is increasing for type 2 diabetes, whereas, encouragingly, a declining number is seen in type 1 diabetes, at least in Scandinavia. The cumulative incidence of proteinuria was previously estimated to be ∼40%, but it is less now, at least in type 1 diabetes, but figures vary from one country to another.

Increased basement membrane thickness and mesangial expansion are hallmarks of glomerulopathy, but on the molecular level the exact renal locus or loci as well as detailed mechanisms for development of diabetic renal disease remain unclear, whereas it is well established that the major risk factors for development of nephropathy are poor glycemic control and elevated blood pressure. In particular, the two in combination, the so-called “double jeopardy,” is critical (1), but the concept of a dual jeopardy may have led to some confusion.

Some patients who have poor glycemic control escape nephropathy, but such patients seem to have low blood pressure in long-term follow-up studies, also supporting the concept of dual jeopardy (2). A single risk factor like hyperglycemia may thus not always be sufficient to provoke clinical nephropathy. The cumulative absence of nephropathy in 60–80% of patients …
Glomerular Deposition of Properdin in Henoch-Schonlein Syndrome and Idiopathic Focal Nephritis
Authors: D. J. Evans, D. G. Williams, D. K. Peters, J. G. P. Sissons, J. M. Boulton-Jones, C. S. Ogg, J. S. Cameron, B. I. Hoffbrand
Journal: BMJ (1973)

Biopsy of renal tissue from four patients with idiopathic focal nephritis and three patients with Henoch-Schönlein syndrome showed that C3 and properdin were deposited with IgA in the glomerular mesangium, C1q could not be detected. These observations suggest that glomerular injury in disorders characterized by mesangial deposits of IgA and C3 is mediated via the properdin system.