tbuckley/cabot-search huggingface dataset:
Quantitative Multiplex Methylation-Specific PCR Analysis Doubles Detection of Tumor Cells in Breast Ductal Fluid
Authors: Mary Jo Fackler, Kara Malone, Zhe Zhang, Eric Schilling, Elizabeth Garrett-Mayer, Theresa Swift-Scanlan, Julie Lange, Ritu Nayar, Nancy E. Davidson, Seema A. Khan, Saraswati Sukumar
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The challenges of cytology for accurate diagnosis of breast cancer are well recognized. We previously showed that normal and tumor tissue can be distinguished using a technique called quantitative multiplex methylation-specific PCR (QM-MSP). We hypothesized that quantitative analysis of methylated genes will provide enhanced detection of cancer cells present in cytologic specimens. Experimental Design: QM-MSP was done on ductal lavage cells from a set of 37 ductal lavage samples from women undergoing mastectomy (27 with cancer and 3 without). Duct histology information was available for each lavaged duct. QM-MSP data was assessed by measuring cumulative methylation index and by receiver operating characteristic threshold analysis. To determine the baseline level of methylation for each gene in this population, cells from 60 ducts of women at high risk of developing breast cancer were analyzed. Results: QM-MSP findings on a panel of nine genes were correlated to duct histology and ductal lavage cytology. Cytology detected cancer in 33% (7 of 21 ducts) with a specificity of 99% (92 of 93). QM-MSP detected cancer as calculated by cumulative methylation index with a sensitivity of 62% (13 of 21) and specificity of 82% (62 of 76) and by receiver operating characteristic threshold analysis with a sensitivity of 71% (15 of 21) and specificity of 83% (63 of 76). Conclusions: Compared with cytology, QM-MSP doubled the sensitivity of detection of cancer. This study provides proof of principle by showing the advantages of using methylation analyses to query cytologic specimens and indicates its potential use in diagnosis and in stratifying risk.
Functional characterisation of the CFTR mutations M348V and A1087P from patients with pancreatitis suggests functional interaction between CFTR monomers
Authors: F U Weiss, P Simon, N Bogdanova, N Shcheynikov, S Muallem, M M Lerch
Journal: Gut (2009)

In a recent study on the role of cystic fibrosis transmembrane conductance regulator (CFTR) mutations in idiopathic chronic pancreatitis ( Gut 2005; 54 :1456–60) we sequenced the complete CFTR-coding region of 67 pancreatitis patients and 60 controls. The study demonstrated that even carrier status for mild or uncommon CFTR mutations increases the risk for developing pancreatitis. Two patients with previously unknown CFTR mutations (M348V and A1087P) were identified, and their unexpected clinical course after conclusion of the trial prompted the functional studies below.

The M348V mutation was found in a woman diagnosed with chronic pancreatitis at the age of 63. Following drainage of a pseudocyst the patient suffered from recurrent episodes of pancreatitis and later died from breast cancer. The patient with the A1087P mutation was recruited to the study as a 19 year old with idiopathic chronic pancreatitis and exocrine pancreatic insufficiency. When a later operation to correct a funnel chest did not result in a complete resolution of her expiratory flow limitation she underwent additional tests. An ambiguous sweat chloride test together with the presence of a ΔF508 mutation (inherited from her healthy mother) and the novel A1087P mutation (inherited from her healthy father) suggest that this patient suffers from a mild variety of cystic fibrosis rather than from idiopathic chronic pancreatitis, as initially thought. We therefore decided to …
Tumorigenic and Metastatic Activity of Human Thyroid Cancer Stem Cells
Authors: Matilde Todaro, Flora Iovino, Vincenzo Eterno, Patrizia Cammareri, Guido Gambara, Virginia Espina, Gaspare Gulotta, Francesco Dieli, Silvia Giordano, Ruggero De Maria, Giorgio Stassi
Journal: Cancer Research (2010)

Thyroid carcinoma is the most common endocrine malignancy and the first cause of death among endocrine cancers. We show that the tumorigenic capacity in thyroid cancer is confined in a small subpopulation of stem-like cells with high aldehyde dehydrogenase (ALDH(high)) activity and unlimited replication potential. ALDH(high) cells can be expanded indefinitely in vitro as tumor spheres, which retain the tumorigenic potential upon delivery in immunocompromised mice. Orthotopic injection of minute numbers of thyroid cancer stem cells recapitulates the behavior of the parental tumor, including the aggressive metastatic features of undifferentiated thyroid carcinomas, which are sustained by constitutive activation of cMet and Akt in thyroid cancer stem cells. The identification of tumorigenic and metastagenic thyroid cancer cells may provide unprecedented preclinical tools for development and preclinical validation of novel targeted therapies.
Nitric Oxide Upregulates Induction of PDGF Receptor-α Expression in Rat Renal Mesangial Cells and in Anti-Thy-1 Glomerulonephritis
Authors: Karl-Friedrich Beck, Gülmisal Güder, Liliana Schaefer, Miriam Pleskova, Andrea Babelova, Meik H Behrens, Daniel Mihalik, Martina Beck, Roland M Schaefer, Josef Pfeilschifter
Journal: Journal of the American Society of Nephrology (2005)

PDGF and nitric oxide (NO) have been shown to participate in the progression of several forms of glomerulonephritis. A potential influence of NO on PDGF-mediated signaling cascades was therefore examined. Treatment of rat mesangial cells (MC) with the NO donors diethylenetriamine NO (DETA-NO) or spermine-NONOate resulted in a time- and dose-dependent upregulation of PDGF receptor alpha (PDGFRalpha) but not PDGFRbeta mRNA levels. Administration of DETA-NO also induced PDGFRalpha protein expression that was paralleled also by an enhanced receptor phosphorylation. Further experiments using 3-(5-hydroxymethyl-2-furyl)-1-benzylindazole (YC-1), an activator of the soluble guanylyl cyclase (sGC), the membrane-soluble cyclic GMP (cGMP) analog 8-Bromo-PET-cGMP, and the inhibitors of sGC ODQ and NS2028 suggest that elevated cGMP levels are responsible for the effects of NO. Importantly, NO-dependent autophosphorylation of PDGFRalpha drastically augmented PDGF-AA-evoked phosphorylation of PKB/Akt, a classical downstream target of PDGFRalpha signaling. Furthermore, in a rat model of anti-Thy-1 glomerulonephritis, expression and phosphorylation of PDGFRalpha but not PDGFRbeta expression was markedly reduced in nephritic animals that were treated with the inducible NO synthase inhibitor L-N6(1-iminoethyl)lysine(dihydrochloride) (L-NIL) compared with non-L-NIL-treated nephritic rats as demonstrated by Western blotting and immunohistochemistry. Taken together, the data suggest that NO modulates PDGFRalpha-triggered signaling in a cGMP-dependent manner by induction of PDGFRalpha expression in MC and in a rat model of mesangioproliferative glomerulonephritis. The mechanistic details of this regulation have to be elucidated in further experiments.
Patient selection for laparoscopic excision of adrenal metastases: A multicenter cohort study
Authors: Alexandre Gryn, Benoit Peyronnet, Andréa Manunta, Jean-Baptiste Beauval, Elie Bounasr, François-Xavier Nouhaud, Nathalie Rioux-Leclercq, Philippe Caron, Mathieu Thoulouzan, Grégory Verhoest, Michel Soulie, Karim Bensalah, Eric Huyghe
Journal: International Journal of Surgery (2015)
The PIM1 Kinase Shows Genome Driven Upregulation, Suppresses Apoptosis, Enables Colony Formation and Cell Migration and is a Potential Target in Triple-Negative Breast Cancer
Authors: F. Brasó Maristany, A. Grigoriadis, E. Noël, P. Gazinska, E. de Rinaldis, S. Pinder, P. Marra, A. Tutt
Journal: Annals of Oncology (2013)
Contact allergy to 8-methoxypsoralen
Authors: I. WEISSMANN, G. WAGNER, G. PLEWIG
Journal: British Journal of Dermatology (1980)

A 20-year-old male patient was treated topically with 8-methoxypsoralen and long-wave ultraviolet light (UV-A) for alopecia areata. He developed contact allergy to 8-methoxypsoralen after the sixth treatment (day 17), which was verified by patch testing and histopathology.
The effect of osseous ankle configuration on chronic ankle instability
Authors: Arno Frigg, Olaf Magerkurth, Victor Valderrabano, Hans-Peter Ledermann, Beat Hintermann
Journal: British Journal of Sports Medicine (2007)

Background: Chronic ankle instability (CAI) is a common orthopaedic entity in sport. Although other risk factors have been studied extensively, little is known about how it is influenced by the osseous joint configuration. Aim: To study the effect of osseous ankle configuration on CAI. Design: Case–control study, level III. Setting: Radiological examination with measurement of lateral x rays by an independent radiologist using a digital DICOM/PACS system. Patients: A group of 52 patients who had had at least three recurrent sprains was compared with an age-matched and sex-matched control group of 52 healthy subjects. Main outcome measures: The radius of the talar surface, the tibial coverage of the talus (tibiotalar sector) and the height of the talar body were measured. Results: The talar radius was found to be larger in patients with CAI (21.2 (2.4) mm) than in controls (17.7 (1.9) mm; p&lt;0.001, power &gt;95%). The tibiotalar sector, representing the tibial coverage of the talus, was smaller in patients with CAI (80° (5.1°)) than in controls (88.4° (7.2°); p&lt;0.001, power &gt;95%). No significant difference was observed in the height of the talar body between patients with CAI (28.8 (2.6) mm) and controls (27.5 (4.0) mm; p = 0.055). Conclusion: CAI is associated with an unstable osseous joint configuration characterised by a larger radius of the talus and a smaller tibiotalar sector. There is evidence that a higher talus might also play some part, particularly in women.
Predominance of type I 5α‐reductase in apocrine sweat glands of patients with excessive or abnormal odour derived from apocrine sweat (osmidrosis)
Authors: None Sato, None Sonoda, None Itami, None Takayasu
Journal: British Journal of Dermatology (1998)

High levels of 5α-reductase activity have been detected in human apocrine glands, and the concentration of dihydrotestosterone has been found to be higher than that of testosterone in the nuclear fraction of the skin of patients who suffer from excessive or abnormal odour derived from apocrine sweat (osmidrosis). Although these results suggest that 5α-reductase may play a central role in the action of androgens in the apocrine gland, the isozyme responsible is not known. We therefore assayed 5α-reductase type I and type II activity and mRNA expression in isolated apocrine glands from four patients with osmidrosis. When we incubated gland homogenates with [3H]testosterone, we found that the biochemical properties of the apocrine gland enzyme were consistent with those of type I 5α-reductase: at substrate concentrations of both 50 nmol/L and 1 μmol/L, the optimum pH was in the range 6.0–7.5, and the apparent Km was 21.1 μmol/L. The apocrine gland enzyme was inhibited by MK386, a specific inhibitor of type I 5α-reductase, in a dose-dependent manner, but it was hardly affected by finasteride, a specific inhibitor of type II isozyme, in that a nanomolar concentration of finasteride produced only a slight inhibition. Reverse transcriptase–polymerase chain reaction showed that the apocrine gland expressed type I 5α-reductase mRNA exclusively, except for a faint band of type II isozyme in a few preparations. These data indicate that the type I isozyme is the predominant form of 5α-reductase in the apocrine gland and may play a central role in the anabolic activity of androgens, as reported for the sebaceous gland. In addition, a small amount of type II isozyme may be expressed by mesenchymal cells that surround the apocrine glands and also contribute to their development.
Mucosal sulfhydryl compounds evaluation by in vivo electron spin resonance spectroscopy in mice with experimental colitis
Authors: H Togashi
Journal: Gut (2003)

Sulfhydryl (SH) compounds are essential in maintaining mucosal integrity in the gastrointestinal tract. A decrease in colonic mucosal SH compounds affects the redox status of the mucosa, resulting in vulnerability to further attacks. Therefore, there is a strong need for in vivo evaluation of SH compounds in the colonic mucosa.The aim of the current study was to establish a method of evaluating levels of SH compounds in the colonic mucosa of live animals before and after induction of colitis.Murine experimental colitis was induced by instillation of trinitrobenzene sulphonic acid (TNBS) dissolved in 50% ethanol into the colon via the anus. For evaluation of mucosal SH compounds in the colon, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL), a stable nitroxide radical, was instilled into the colonic lumen of live mice and the spin clearance rate was measured by L-band electron spin resonance (ESR) spectroscopy.Morphological study showed that mucosal damage was severe one or two days after TNBS instillation. The colonic mucosa started to regenerate at four days, and looked normal at seven days, after induction of colitis. The spin clearance rate of carbamoyl-PROXYL decreased significantly at 0.5, 1, 2, and 4 days after induction of colitis compared with mice before TNBS instillation. Surprisingly, although the colonic mucosa looked normal seven days after TNBS administration, the spin clearance rate still remained significantly slow. The spin clearance rate returned to normal 14 days after induction of colitis. The change in in vivo spin clearance rate was consistent with the time dependent change in mucosal reduced glutathione, a major component of SH compounds.The spin clearance rate obtained by L-band ESR spectroscopy in combination with carbamoyl-PROXYL can give an estimate of the level of colonic mucosal SH compounds in live animals and is useful for evaluating the mucosal defence system against oxidative stress.
Biliary excretion of glutathione and glutathione disulfide in the rat. Regulation and response to oxidative stress.
Authors: B H Lauterburg, C V Smith, H Hughes, J R Mitchell
Journal: Journal of Clinical Investigation (1984)

Regulation of the biliary excretion of reduced glutathione (GSH) and glutathione disulfide (GSSG) and responses to selected model toxins were examined in male Sprague-Dawley rats. In control and phenobarbital-pretreated rats in which the intrahepatic concentration of GSH was modulated by the administration of diethyl maleate or acetaminophen, the biliary concentration of GSH was consistently lower than, but directly proportional to, the intrahepatic concentration of GSH. Furthermore, increments in bile flow produced by the infusion of sulfobromophthalein (BSP)-glutathione were associated with proportional increases in the biliary excretion of GSH, suggesting that GSH passes into bile passively along a concentration gradient. In contrast, GSSG appears to be secreted into bile against a steep concentration gradient. An increased hepatic production and biliary excretion of GSSG resulted from the administration of t-butyl hydroperoxide. Measurement of biliary GSSG and BSP during a constant infusion of the GSH adduct of BSP indicated that GSSG shares a common excretory mechanism with GSH adducts. Diquat, nitrofurantoin, and paraquat also markedly stimulated the biliary excretion of GSSG. On a molar basis, these compounds generated much more GSSG than a direct substrate for glutathione peroxidase such as t-butyl hydroperoxide, indicating that the compounds undergo redox-cycling with concomitant production of hydrogen peroxide. Aminopyrine (0.8 mmol/kg) also significantly increased biliary GSSG. This increase, however, was associated with a proportional increase in bile flow and in the biliary excretion of GSH such that the GSSG/GSH ratio in bile did not change. Acetaminophen and chloroform, two compounds generating electrophilic metabolites that deplete intrahepatic GSH, led to a progressive decrease in the biliary excretion of GSH and GSSG. Furosemide and dimethylnitrosamine, the electrophilic metabolites of which do not deplete hepatic GSH, minimally altered biliary GSH and GSSG. Similarly, carbon tetrachloride and iproniazid, which yield organic radical metabolites that can peroxidize membrane lipids, did not increase the biliary excretion of GSSG. This finding indicates that membrane-bound lipid hydroperoxides may not be good substrates for glutathione peroxidases. The measurement of the biliary excretion of GSSG and of the GSSG/GSH ratio in bile is a sensitive index of oxidative stress in vivo and thus complements other in vivo parameters for the study of reactive intermediates of xenobiotics such as the determination of covalent binding, the formation of lipid hydroxy acids, and the depletion of intracellular GSH.
Control versus causation of addiction
Authors: Kent C. Berridge, Terry E. Robinson
Journal: Behavioral and Brain Sciences (1996)

Abstract Heyman explains useful ways to bring addictive drug use under environmental control. We doubt that relapse is explained by drug features such as immediate reinforcement, clouding of judgment, and so forth. Relapse may require explanation in terms of enduring sensitization of incentive neural substrates, but even if its causal assumptions are wrong, Heyman's model makes useful predictions for behavioral control.
Lung Function Decline and Outcomes in an Adult Population
Authors: David M. Mannino, Matthew M. Reichert, Kourtney J. Davis
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality.Objectives: To determine risk factors for and outcomes of rapid lung function decline in a cohort of adults in the United States.Methods: We analyzed data from 15,536 adults aged 44–66 yr in the Atherosclerosis Risk in Communities study. We used Cox proportional hazard models to determine the risk of rapid lung function decline at 3 yr on mortality and COPD hospitalizations over the subsequent 8 yr.Measurements and Main Results: Of those in the baseline cohort, 13,756 (88.5%) had spirometry at the Year 3 visit. The strongest risk factors for not having a follow-up spirometry were as follows: having Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 3 or 4 disease at baseline (adjusted odds ratio [OR] 2.8; 95% confidence interval [CI], 2.1–3.8), being black (adjusted OR, 2.4; 95% CI, 2.1–2.7), and being a current smoker (adjusted OR, 1.8; 95% CI, 1.5–2.0). Participants with GOLD stage 3 or 4 disease were also more likely to be in the most rapidly declining lung function quartile (adjusted OR, 3.7; 95% CI, 2.7–5.0). Overall, participants with the most rapidly declining lung function had a modestly increased risk of death (adjusted hazard ratio, 1.4; 95% CI, 1.2–1.7) and time to a COPD-related hospitalization (adjusted hazard ratio, 1.4; 95% CI, 1.2–1.8).Conclusion: Rapid lung function decline was independently associated with a modest increased risk of COPD hospitalizations and deaths.
Cochlear Implantation for the Treatment of Deafness
Authors: Benjamin J. Copeland, Harold C. Pillsbury
Journal: Annual Review of Medicine (2004)

Cochlear implants have dramatically changed the treatment and prognosis for patients with profound sensorineural hearing loss. Deaf adults and children can be successfully (re)integrated into the hearing world through a multidisciplinary approach involving otolaryngologists, audiologists, and speech/language pathologists. As the technology of the cochlear prosthesis advances, the candidacy for these devices continues to broaden. This review addresses the basic technology, candidacy criteria, and important issues in the fields of adult and pediatric cochlear implantation. Cost utility and future directions in the treatment of the profoundly hearing impaired are discussed.
A systematic literature review of drug therapies for the treatment of psoriatic arthritis: current evidence and meta-analysis informing the EULAR recommendations for the management of psoriatic arthritis
Authors: Zoe Ash, Cécile Gaujoux-Viala, Laure Gossec, Elizabeth MA Hensor, Oliver FitzGerald, Kevin Winthrop, Désirée van der Heijde, Paul Emery, Josef S Smolen, Helena Marzo-Ortega
Journal: Annals of the Rheumatic Diseases (2011)

Objectives To review the available evidence for the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), synthetic and biological drug therapies for the different clinical manifestations of psoriatic arthritis (PsA) in order to provide data for the development of treatment recommendations by the European League Against Rheumatism (EULAR) taskforce. Methods A systematic literature review (SLR) of available treatments for PsA was performed using the largest electronic databases (MEDLINE, EMBASE and COCHRANE) by two working groups formed within the EULAR taskforce. This comprised a comprehensive sample of rheumatologists, dermatologists, epidemiologists and patients. The available evidence was reviewed for NSAIDs, synthetic disease modifying antirheumatic drugs (DMARDs), local and systemic corticosteroids and biologic drugs. All articles and abstracts published between 1962 and January 2010 were reviewed and considered and a meta-analysis of data on biological therapies was performed. Results While little data are available on NSAIDs, glucocorticoids and synthetic DMARDs, the available evidence suggests an acceptable efficacy and safety profile of both NSAIDs and synthetic DMARDs (methotrexate, cyclosporine A, sulfasalazine and leflunomide) in PsA. More evidence is available (level 1B) supporting the efficacy of anti-tumour necrosis factor (anti-TNF) agents (adalimumab, etanercept, golimumab and infliximab) in treating the signs and symptoms of PsA as well as reducing radiographic progression. Registry data show no new safety concerns, although the numbers studied to date are relatively small. Conclusions This SLR reveals some evidence to support the use of NSAIDs and synthetic DMARDs and good evidence for the efficacy of anti-TNF therapy in PsA.
Relationship between silicosis and rheumatoid arthritis.
Authors: G K Sluis-Cremer, P A Hessel, E Hnizdo, A R Churchill
Journal: Thorax (1986)

The relationship between rheumatoid arthritis and silicosis was studied by means of a case-control study in South African gold miners. One hundred and fifty seven miners with rheumatoid arthritis classified as "definite" (91) or "probable" (66) were individually matched by year of birth with miners who had no evidence of rheumatoid arthritis. Unmatched analysis of the case-control status for "probable" and "definite" cases yielded an odds ratio of 2.84 (p = 0.0001). Separate analyses yielded an odds ratio of 3.79 (p = 0.0006) for "definite" cases, a non-significant odds ratio for "probable" cases, and an odds ratio of 5.00 (p = 0.0003) for the presence of rheumatoid factor. These results could not be explained on the basis of cumulative dust exposure or intensity of exposure. The rate of progression of silicosis in both the "definite" and the "probable" groups was greater than for the control patients with silicosis, as was the probability of silicosis presenting at the start with larger nodules (type r).