tbuckley/cabot-search huggingface dataset:
Beneficial Effects of Long-Term Use of the Antioxidant Probucol in Heart Failure in the Rat
Authors: Ying Tung Sia, Nathalie Lapointe, Thomas G. Parker, James N. Tsoporis, Christian F. Deschepper, Angelino Calderone, A. Pourdjabbar, J.F. Jasmin, J.F. Sarrazin, Peter Liu, Albert Adam, Jagdish Butany, Jean L. Rouleau
Journal: Circulation (2002)

Congestive heart failure (CHF) is a disease that is characterized by progressive left ventricular (LV) dysfunction and dilatation. Oxidative stress is thought to contribute to the progression of CHF, and antioxidants have been shown to have beneficial effects when started early after myocardial infarction (MI). In this study, we tested whether the powerful antioxidant probucol would attenuate progression of CHF once it was established after MI in the rat.Ligation of a coronary artery was used to create an MI in rats (n=266). Survivors were then randomized 20 days after MI to either probucol 61 mg. kg(-1). d(-1) or vehicle and followed up for a total of 100 days after MI. Studies of cardiac hemodynamics, LV remodeling, cardiac apoptosis and morphology, systemic neurohumoral activation, oxidative stress, and renal function were then evaluated. Probucol improved LV function (LV maximum rate of pressure rise from 3103 to 4250 mm Hg/s, P<0.05, and LV end-diastolic pressure decrease from 28 to 24 mm Hg, P<0.05), reduced pulmonary weights, prevented right ventricular systolic hypertension, and preserved renal function compared with vehicle. Probucol also prevented LV dilatation, prevented wall thinning (1.70 versus 1.42 mm, P<0.05), reduced cardiac fibrosis and cardiac apoptosis, attenuated increased myocardial cell cross-sectional area, and increased scar thickness.In chronic CHF, probucol exerts multiple beneficial morphological effects that result in better LV remodeling and function, reduced neurohumoral activation, and preserved renal function.
ACTH-secreting 'apudoma' of gallbladder.
Authors: R W Spence, C J Burns-Cox
Journal: Gut (1975)

The case of a 44-year-old woman is reported. The diagnosis after the appropriate tests and laparotomy was ACTH-secreting 'apudoma' of the gallbladder. This is a rare tumour and this case is believed to be the first reported of an ectopic hormone producing tumour from this side.
Tuberculin response in BCG vaccinated schoolchildren and the estimation of annual risk of infection in Hong Kong
Authors: C C Leung
Journal: Thorax (2005)

In Hong Kong there has been nearly universal neonatal BCG vaccination coverage since 1980.21 113 schoolchildren aged 6-9 years were skin tested with one unit of tuberculin (PPD RT-23) using the intradermal technique during a routine BCG revaccination programme. Information on sex, date of birth, date of tuberculin testing, and tuberculin reaction size at 72 hours was retrieved. The annual risk of tuberculous infection (ARTI) was estimated by three different approaches.Significantly higher tuberculin positive rates were found in girls and with increasing age at all commonly used cut-off points (5, 10, and 15 mm). Using a cut-off point of > or =10 mm and the formula 1- (1 - tuberculin positive rate)(1/age), the ARTI was estimated to be 1.93% (95% CI 1.84 to 2.03) for girls and 1.41% (95% CI 1.33 to 1.50) for boys. Using the differences in the tuberculin positive rate between the 6-7 year and 8-9 year age groups, the ARTI became 1.90% (95% CI 1.09 to 2.70) and 1.84% (95% CI 1.15 to 2.54) for girls and boys, respectively. When the prevalence of infection was estimated by locating a secondary peak of the tuberculin reaction distribution curve at 15 mm and assuming a symmetrical distribution of reaction sizes among those infected around this peak, the corresponding ARTI was much lower at 0.52% (95% CI 0.46 to 0.59) and 0.43% (95% CI 0.37 to 0.49) for girls and boys, similar to that estimated indirectly from the prevalence of disease.The ARTI as estimated by conventional methods was unexpectedly high among BCG vaccinated children and did not agree with that anticipated from the annual incidence of active disease. Further studies are needed to address the discrepancies, including the possible interaction between BCG and other environmental stimuli.
Podocin Participates in the Assembly of Tight Junctions between Foot Processes in Nephrotic Podocytes
Authors: Akemi Shono, Hiroyasu Tsukaguchi, Eishin Yaoita, Masaaki Nameta, Hidetake Kurihara, Xiao-Song Qin, Tadashi Yamamoto, Toshio Doi
Journal: Journal of the American Society of Nephrology (2007)

The predominant type of cellular junction between normal podocyte foot processes is the slit diaphragm. Under nephrotic conditions,however, foot process effacement leads to the loss of slit diaphragms and the new formationof tight junctions composed of the proteins coxsackievirus and adenovirus receptor (CAR) and zonula occludens 1 (ZO-1). Podocin, a protein that plays a key role in maintaining the integrity of the slit diaphragm, has also been localized to these tight junctions, but its function at this site is unknown. In this study, we confirmed that podocin colocalizes with CAR and ZO-1 at the tight junction between foot processes in nephrotic rats. Using primary cultures of rat podocytes, as well as cell lines that co-expressed podocin and CAR, we observed that podocin was recruited to sites of cell-cell contact and that it co-localized with CAR and ZO-1. Immunoprecipitation suggested that these three junctional proteins from a multi-protein complex. Consistent with this, we found that podociin facilitated the coalescence of preassembled lipid rafts containing CAR and restricted their lateral mobility, the latter likely a result of dynamic actin reorganization and subsequent tethering of CAR-podocin complexes to the cytoskeleton. In conclusion, in addition to serving as a structural protein of the slit diaphragm of normal podocytes, our data suggest that podocin may also serve as a scaffold that links tight junction proteins to the actin cytoskeleton in nephrotic foot processes.
Pharmacokinetics of terbinafine in the nail
Authors: A.Y. FNLAY
Journal: British Journal of Dermatology (1992)

Oral terbinafine is an effective therapy for dermatophyte onychomycosis, presumably because it reaches the infected areas of the nail rapidly and in fungicidal concentrations. For planning optimal clinical dosage regimes, it is necessary to know the rate of terbinafine movement through the nail plate, the concentrations achieved, and the persistence in the nail plate after stopping treatment. In a study of 12 patients receiving terbinafine at 250 mg/day for up to 48 weeks, measurement of terbinafine in distal nail clippings demonstrated that the drug was first detectable 3-18 weeks after starting therapy. A level of 0.25-0.55 ng/mg was quickly achieved and remained stable. Concentrations of terbinafine in distal clippings of unaffected nails were similar to those in affected nails. Although the average nail concentrations are within the fungicidal range for dermatophytes, the anatomy of an infected nail may result in relatively protected areas of infection. This results in the occasional persistence or recurrence of dermatophytic infection observed in some cases. However, the results of this study justify further trials of 'short-term' oral terbinafine therapy for onychomycosis. A current study is addressing the relationship of oral dosage to nail drug concentration and its later persistence in the nail plate.
Using Marketing Muscle to Sell Fat: The Rise of Obesity in the Modern Economy
Authors: Frederick J. Zimmerman
Journal: Annual Review of Public Health (2011)

The large increase in obesity in the past 30 years has often been explained in rational choice terms; for example, a decline in food prices has engendered greater food consumption. On closer examination, this kind of explanation does not fit the facts of the current obesity epidemic. Instead, an unprecedented expansion in the scope, power, and ubiquity of food marketing has coincided with an unprecedented expansion in food consumption in predictable ways. Ongoing protestations that the causes of the recent increase in obesity are unknown may overstate the case. Ample evidence indicates that the obesity epidemic is, at least to a large degree, the result of increased marketing power over the American diet. Only by reigning in or countering marketing power can rationality be restored to the dietary choices of Americans.
Viewpoints on the Way to the Consensus Session
Authors: Patricia Iozzo
Journal: Diabetes Care (2009)

Adipose tissue is a heterogeneous organ with respect to embryonic origin, body distribution, and function. In addition to playing a major role in the regulation of nutrient and energy homeostasis, it is involved in the modulation of the immune response, reproductive function, hemostasis, mechanical support, bone mass growth, and thermogenesis.

To postulate that insulin resistance starts in adipose tissue, there should be evidence of 1 ) potential mechanisms for such a causal relationship, 2 ) the manifestation of such mechanisms in insulin-resistant individuals, and 3 ) their early occurrence in the development of insulin resistance.

Adipose tissue releases a variety of factors known to modulate insulin sensitivity, and their effects are summarized in Fig. 1.



Figure 1 
Adipose tissue is the largest endocrine organ in the body. The diagram summarizes the main roles and effects of representative fat-derived products that have been related to insulin resistance and metabolic risk. BP, blood pressure; HR, heart rate.



### Fatty acids

The concept that fatty acids (FAs) provoke cardiac, skeletal muscle, and hepatic insulin resistance and impair β-cell function has been extensively confirmed in humans, and mechanisms are reviewed in detail elsewhere (1). A sustained pharmacologic inhibition of lipolysis, with reduction in the plasma FA concentration, reverses these defects (2–4). Elevated FA levels also promote the synthesis and release of VLDL by the liver by 1 ) increasing substrate availability, 2 ) inhibiting insulin-mediated apoB degradation (5), and 3 ) reducing hepatic insulin clearance, contributing to hyperinsulinemia. In the brain, excessive FA uptake and its response to weight loss have been documented in subjects with the metabolic syndrome (6), and FAs are implicated in the central regulation of glucose production (7).

FA overflow from adipocytes to skeletal muscle and other tissues may result in free radical formation during oxidative phosphorylation, the intramyocellular accumulation of triglyceride, and the production of toxic …
The mouse genome sequence - the end of the tail, or just the beginning?
Authors: Janet Rossant, Stephen W Scherer
Journal: Genome biology (2003)

The recent flurry of papers on the mouse genome includes the description of the full genome assembly, analysis of the mouse transcriptome, the origin of interstrain variation, initial analysis of conserved non-coding regions and high-throughput expression analysis of a subset of genes. Each illustrates how the availability of the genome sequence will change the way mouse biologists do business in future.
Does Incomplete Recovery From First Lifetime Major Depressive Episode Herald a Chronic Course of Illness?
Authors: L L Judd, M J Paulus, P J Schettler, H S Akiskal, J Endicott, A C Leon, J D Maser, T Mueller, D A Solomon, M B Keller
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: This study investigated the influence of incomplete recovery from first lifetime major depressive episodes on long-term outcome. METHOD: After their first lifetime major depressive episode, patients were divided into asymptomatic (N=70) and residual subthreshold depressive symptom (N=26) recovery groups and compared on longitudinal course during up to 12 years of prospective naturalistic follow-up. RESULTS: Patients with residual subthreshold depressive symptoms during recovery had significantly more severe and chronic future courses. Those with residual symptoms relapsed to major and minor depressive episodes faster and had more recurrences, shorter well intervals, and fewer symptom-free weeks during follow-up than asymptomatic patients. CONCLUSIONS: Resolution of major depressive episodes with residual subthreshold depressive symptoms, even the first lifetime episode, appears to be the first step of a more severe, relapsing, and chronic future course. When ongoing subthreshold symptoms continue after major depressive episodes, the illness is still active, and continued treatment is strongly recommended.
Effective gene therapy with nonintegrating lentiviral vectors
Authors: Rafael J Yáñez-Muñoz, Kamaljit S Balaggan, Angus MacNeil, Steven J Howe, Manfred Schmidt, Alexander J Smith, Prateek Buch, Robert E MacLaren, Patrick N Anderson, Susie E Barker, Yanai Duran, Cynthia Bartholomae, Christof von Kalle, John R Heckenlively, Christine Kinnon, Robin R Ali, Adrian J Thrasher
Journal: Nature Medicine (2006)
Consultant staffing and career prospects in gastroenterology for England and Wales. Royal College of Physicians Committee for Gastroenterology and Clinical Services Committee of the British Society of Gastroenterology.
Authors: G Neale, R Williams
Journal: Gut (1993)

In the three years since the last report on career prospects in medical gastroenterology in England and Wales' the need for more specialist gastroenterologists has become increasingly evi- dent.In part this is because of an increased demand for endoscopy2; and in particular the development of laparoscopic cholecystectomy which has expanded requirements for endoscopic retrograde cholangiopancreatography (ERCP).Five years ago it was suggested that ERCP would be limited to larger centres; now it is required in every district general hospital of average size.In addition liver transplantation is becoming a routine procedure and Newcastle is soon to be added to the five centres already offering this surgical solution to liver failure and end stage liver disorders.Hepatologists are required, not only for the development of transplant centres, but also throughout the country for the accurate assessment of patients with liver disease.Finally, specialist gastroenterologists are playing a major role in developing the services for artificial nutritional support.3Recently pub- lished evidence shows that gastroenterologists are undertaking more service sessions than con- sultants in other general medical specialities45 and, on average, work well above scheduled hours.Thus there is strong evidence to support a further expansion in consultant staffing for gastroenterology.
Long-standing groin pain in sportspeople falls into three primary patterns, a “clinical entity” approach: a prospective study of 207 patients
Authors: Per Hölmich
Journal: British Journal of Sports Medicine (2007)

Background: Groin pain remains a major challenge in sports medicine. Aim: To examine 207 consecutive athletes (196 men, 11 women) with groin pain using a standardised and reliable clinical examination programme that focused on signs that suggest pathology in (1) the adductors, (2) the ilopsoas and (3) the rectus abdominis. Patients and methods: Most patients were football players (66%) and runners (18%). In this cohort, the clinical pattern consistent with adductor-related dysfunction, was the primary clinical entity in 58% of the patients and in 69% of the football players. Iliopsoas-related dysfunction was the primary clinical entity in 36% of the patients. Rectus abdominis-related dysfunction was found in 20 (10%) patients but it was associated with adductor-related pain in 18 of these patients. Multiple clinical entities were found in 69 (33%) patients; of these, 16 patients had three clinical entities. Conclusions: These descriptive data extend previous findings that physical examination for groin pain can be reliable. While underscoring the prevalence of adductor-related physical examination abnormality in football players, the data highlight the prevalence of examination findings localising to the iliopsoas among this cohort. Also, the fact that combinations of clinical entities were present has important implications for treatment. The finding of multiple abnormal clinical entities also raises the possibility that earlier presentation may be prudent; it is tempting to speculate that one clinical entity likely precedes other developing entities. These data argue for the need for a trial where clinical entities are correlated with systematic investigation including MRI and ultrasonography.
Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7
Authors: Régis Peffault de Latour, Hélène C. Dujardin, Florence Mishellany, Odile Burlen-Defranoux, Julien Zuber, Rute Marques, James Di Santo, Ana Cumano, Paulo Vieira, Antonio Bandeira
Journal: Blood (2006)
Cotranslational endoplasmic reticulum assembly of FcεRI controls the formation of functional IgE-binding receptors
Authors: Edda Fiebiger, Domenico Tortorella, Marie-Helene Jouvin, Jean-Pierre Kinet, Hidde L. Ploegh
Journal: The Journal of Experimental Medicine (2005)

The human high affinity receptor for IgE (FcεRI) is a cell surface structure critical for the pathology of allergic reactions. Human FcεRI is expressed as a tetramer (αβγ2) on basophils or mast cells and as trimeric (αγ2) complex on antigen-presenting cells. Expression of the human α subunit can be down-regulated by a splice variant of FcεRIβ (βvar). We demonstrate that FcεRIα is the core subunit with which the other subunits assemble strictly cotranslationally. In addition to αβγ2 and αγ2, we demonstrate the presence of αβ and αβvarγ2 complexes that are stable in the detergent Brij 96. The role of individual FcεRI subunits for the formation of functional, immunoglobulin E–binding FcεRI complexes during endoplasmic reticulum (ER) assembly can be defined as follows: β and γ support ER insertion, signal peptide cleavage and proper N-glycosylation of α, whereas βvar allows accumulation of α protein backbone. We show that assembly of FcεRI in the ER is a key step for the regulation of surface expression of FcεRI. The ER quality control system thus regulates the quantity of functional FcεRI, which in turn controls onset and persistence of allergic reactions.
Intraperitoneal Bevacizumab (Bev) for Control of Malignant Ascites Due to Advanced-Stage Gastrointestinal Cancers (Gi): a Multicenter Double-Blind, Placebo (Pl)-Controlled, Randomized Phase Ii Study. Aio Sup-0108
Authors: K. Jordan, D. Atanackovic, C. Gog, B. Killing, M. Stahl, W. Freier, D. Arnold, J. Rüssel, A. Hinke, T. Luetkens, S. Wagner, E. Späth-Schwalbe, U. Pelzer, D. Medgenberg, S. Hegewisch-Becker
Journal: Annals of Oncology (2014)
Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project
Authors: C.A. González, F. Megraud, A. Buissonniere, L. Lujan Barroso, A. Agudo, E.J. Duell, M.C. Boutron-Ruault, F. Clavel-Chapelon, D. Palli, V. Krogh, A. Mattiello, R. Tumino, C. Sacerdote, J.R. Quirós, E. Sanchez-Cantalejo, C. Navarro, A. Barricarte, M. Dorronsoro, K.-T. Khaw, N. Wareham, N.E. Allen, K.K. Tsilidis, H. Bas Bueno-de-Mesquita, S.M. Jeurnink, M.E. Numans, P.H.M. Peeters, P. Lagiou, E. Valanou, A. Trichopoulou, R. Kaaks, A. Lukanova-McGregor, M.M. Bergman, H. Boeing, J. Manjer, B. Lindkvist, R. Stenling, G. Hallmans, L.M. Mortensen, K. Overvad, A. Olsen, A. Tjonneland, K. Bakken, V. Dumeaux, E. Lund, M. Jenab, I. Romieu, D. Michaud, T. Mouw, F. Carneiro, C. Fenge, E. Riboli
Journal: Annals of Oncology (2011)
Induction of Bim Expression Contributes to the Antitumor Synergy Between Sorafenib and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase Inhibitor CI-1040 in Hepatocellular Carcinoma
Authors: Da-Liang Ou, Ying-Chun Shen, Ja-Der Liang, Jun-Yang Liou, Sung-Liang Yu, Hsiang-Hsuan Fan, Da-Sheng Wang, Yen-Shen Lu, Chiun Hsu, Ann-Lii Cheng
Journal: Clinical Cancer Research (2009)

Sorafenib has proved survival benefit for patients with advanced hepatocellular carcinoma (HCC). This study explored whether the efficacy of sorafenib can be improved by adding the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor CI-1040 to vertically block the Raf/MEK/ERK pathway.The growth inhibitory effects of sorafenib and CI-1040 were tested in HCC cell lines (Huh-7 and Hep3B) and human umbilical vascular endothelial cells (HUVEC). The potential synergistic growth inhibitory effects were measured by median effect analysis. Apoptosis was measured by flow cytometry. The effects on ERK phosphorylation and levels of apoptosis regulatory proteins were measured by Western blotting. The in vivo antitumor activity of sorafenib and CI-1040 were tested in xenograft HCC models.Combination of sorafenib and CI-1040 synergistically inhibited ERK phosphorylation and cell growth and induced apoptosis in both HCC cells and HUVECs. Increased expression of Bim protein, which correlated with the extent of ERK inhibition, was found in both HCC cells and HUVECs. Knockdown of Bim expression by small interfering RNA partially abrogated the synergistic proapoptotic effects of sorafenib and CI-1040. Combination therapy inhibited tumor growth significantly better than either single agent in the xenograft models.The antitumor effects of sorafenib in HCC can be improved by vertical blockade of Raf/MEK/ERK signaling with CI-1040.
Ultrastructure of the reticular basement membrane in asthmatic adults, children and infants
Authors: S. Saglani, C. Molyneux, H. Gong, A. Rogers, K. Malmström, A. Pelkonen, M. Mäkelä, E. Adelroth, A. Bush, D. N. R. Payne, P. K. Jeffery
Journal: European Respiratory Journal (2006)

Reticular basement membrane (RBM) thickening in asthma is considered to be the result of subepithelial fibrosis. Thus, the RBM in asthma should contain an excess of fibrils identified as interstitial collagen and the ratio of fibril to matrix should be increased above normal levels. Electron micrographs of the RBM were compared with those of interstitial collagen deeper in the bronchial wall using endobronchial biopsy specimens from adult asthmatics (aged 18–41 yrs (n = 10)), children with difficult asthma (aged 6–16 yrs (n = 10)), wheezy infants with reversible airflow limitation (aged 0.3–2 yrs (n = 10)) and age-matched nonasthmatic controls: 10 adults, nine children and nine symptomatic infants with normal lung function. Fibrils in the RBM were significantly thinner (median (range) width 39 (30–52) nm versus 59 (48–73) nm), and fewer fibrils were banded than in the interstitial collagen (ratio of banded to non-banded fibrils 0.08 (0–0.17) versus 0.22 (0–1.3)). The ratio of fibrils to matrix in the thickened RBM of asthmatics did not differ from that of their respective controls (1.34 (0.63–2.49) versus 1.18 (0.31–2.6)). The ratio of fibril to matrix in the thickened reticular basement membrane of asthmatics is normal, and, contrary to what is expected in fibrosis, the fibrils do not resemble those of interstitial collagen.
Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans
Authors: Stephen P. Robertson, Stephen R.F. Twigg, Andrew J. Sutherland-Smith, Valérie Biancalana, Robert J. Gorlin, Denise Horn, Susan J. Kenwrick, Chong A. Kim, Eva Morava, Ruth Newbury-Ecob, Karen H. Ørstavik, Oliver W.J. Quarrell, Charles E. Schwartz, Deborah J. Shears, Mohnish Suri, John Kendrick-Jones, Andrew O.M. Wilkie
Journal: Nature Genetics (2003)
Axillary dissection in breast cancer
Authors: D.J. Boote, A.D. Stockdale, R.H. Phillips, J.S. Tobias, Ian Basnett, Mike Gill, P.J. Hoskin, J.R. Yarnold, S. Milan, U. Chetty, J.Michael Dixon, GeorgeE. Moore, Charles Abernathy, G.T. Royle, A. Farmer, J. Morris, I. Taylor
Journal: The Lancet (1991)