tbuckley/cabot-search huggingface dataset:
ENDOSCOPIC CONTROL OF GASTRODUODENAL HEMORRHAGE
Authors: T O G Kovacs, D M Jensen
Journal: Annual Review of Medicine (1987)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion
Authors: Yasushi Sato, Hironobu Araki, Junji Kato, Kiminori Nakamura, Yutaka Kawano, Masayoshi Kobune, Tsutomu Sato, Koji Miyanishi, Tetsuji Takayama, Minoru Takahashi, Rishu Takimoto, Satoshi Iyama, Takuya Matsunaga, Seiji Ohtani, Akihiro Matsuura, Hirofumi Hamada, Yoshiro Niitsu
Journal: Blood (2005)
The Economic Impact of Diabetes
Authors: Bengt Jonsson
Journal: Diabetes Care (1998)

In assessing the economic impact of diabetes for a population, several factors should be considered, including the incidence and prevalence of the disease, the level of development of the health care system, and the population's overall level of economic development. Two different approaches have been used to address the economic impact of an increasing incidence of diabetes. The first approach uses disability-adjusted life-years (DALYs) to measure intangible costs associated with diabetes. It combines the number of healthy life-years lost as a result of early mortality with those lost because of disability. The second approach, which has been used more frequently, is the cost-of-illness approach, which includes the concepts of direct, indirect, and intangible costs. A study conducted by the World Bank found that of the 1,362 million DALYs lost to all illnesses in 1990, 7.97 million DALYs were lost because of diabetes. In a 1992 study that assessed the direct costs of treating diabetes in the U.S., the American Diabetes Association used the cost-of-illness approach and found that the estimated total expenditure for 1 year was $45.2 billion. The 1994 epidemiological studies by Zimmet and the World Health Organization include estimates of increased prevalence of diabetes resulting from an increase in population. Estimates of the global cost of diabetes based on these studies reveal that diabetes accounts for 2-3% of the total health care budget in every country; therefore, an increase in diabetes incidence and prevalence translates into a significant economic impact.
Absence of Vasomotor Responses to Epinephrine and Arterenol in an Isolated Intracranial Circulation
Authors: HAROLD D. GREEN, ADAM B. DENISON, Arthur T. Hill, Ronald C. Kelly, N. Maxwell Lewis, Bill R. McLain, William S. Myers, F. Byron Smitherman, Lester E. Watts, Arthur F. White
Journal: Circulation Research (1956)

Four experimental procedures were tried with the dog before one was found which enabled us to record vasomotor changes in an intracranial vascular bed, uncomplicated by alteration in vasomotor tone in the extracranial beds. This required extensive dissection and cannulation technics. In experiments in which this was accomplished by complete elimination, on one side, of the communications between the internal carotid artery and the various extracranial arteries, it was demonstrated that doses of epinephrine and arterenol, which have marked vasomotor activity on all other vascular beds, are without effect on the intracranial bed supplied by the internal carotid artery.
VentricularPatch Endocarditis Caused by Propionibacteriumacnes: Advantages of Gallium Scanning
Authors: F. Vandenbos, P.M. Roger, V. Mondain-Miton, B. Dunais, R. Fouché, P. Kreitmann, D. Carles, O. Migneco, P. Dellamonica
Journal: Journal of Infection (2001)
Endometriosis: candidate genes
Authors: I G Campbell, E J Thomas
Journal: Human Reproduction Update (2001)

Endometriosis is generally regarded as a benign disease but it does exhibit some characteristics reminiscent of malignancy. This raises the possibility that, like malignant diseases, the development of endometriosis may involve the acquisition of somatic genetic alterations in genes that regulate cell growth and differentiation. Studies over the past few years have substantiated this view with the identification of a variety of genetic abnormalities usually only associated with malignancies. Our own studies have shown that genetic alterations, as shown by loss of heterozygosity, are relatively common in endometriosis implying that tumour suppressor gene inactivation is likely to be involved in the proliferation and maintenance of all endometriotic implants. We have also shown by DNA fingerprinting that endometriotic lesions found adjacent to ovarian cancers have a common lineage, reinforcing the compelling histological and epidemiological data that endometriosis is a precursor of endometrioid and clear cell ovarian cancers. It is now well accepted that susceptibility to endometriosis may also involve an inherited genetic component. Studies aimed at identifying the predisposing genes are still in their infancy but should eventually provide invaluable insights into the pathology and aetiology of endometriosis.
MEKC of desmosine and isodesmosine in urine of chronic destructive lung disease patients
Authors: S. Viglio, P. Iadarola, A. Lupi, R. Trisolini, C. Tinelli, B Balbi, V Grassi, D Worlitzsch, G Döring, F. Meloni, K.c Meyer, L Dowson, S.l Hill, R.a Stockley, M. Luisetti
Journal: European Respiratory Journal (2000)

Degradation of extracellular matrix components is central to many pathological features of chronic destructive lung disorders. Desmosine and isodesmosine are elastin-derived cross-linked amino acids whose urine levels are considered representative of elastin breakdown. The aim of this study was to apply a novel methodology, based on high-performance capillary electrophoresis, to the quantification of desmosine and isodesmosine in 11 patients with stable chronic obstructive pulmonary disease (COPD), 10 with an exacerbation of COPD, nine with alpha1-antitrypsin deficiency, 13 with bronchiectasis, and 11 adults with cystic fibrosis, in comparison to 24 controls. It was found that, in patients with stable COPD, urinary desmosine levels were higher than in controls (p=0.03), but lower than in COPD subjects with an exacerbation (p&lt; or =0.05). The highest desmosine levels were found in subjects with alpha1-antitrypsin deficiency, bronchiectasis and cystic fibrosis (p&lt;0.001 versus stable COPD). In a short-term longitudinal study, five stable COPD patients showed a constant rate of desmosine excretion (mean coefficient of variation &lt;8% over three consecutive days). In conclusion, the present method is simple and suitable for the determination of elastin-derived cross-linked amino acid excretion in urine, giving results similar to those obtained using other separation methods. In addition, evidence is presented that urinary desmosine excretion is increased in conditions characterized by airway inflammation, such as exacerbations of chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis. Results obtained in subjects with alphal-antitrypsin deficiency suggest that this method might be used to evaluate the putative efficacy of replacement therapy.
Oesophageal mucosal barrier: a key factor in the pathophysiology of non-erosive reflux disease (NERD) and a potential target for treatment
Authors: Philip Woodland, Daniel Sifrim
Journal: Gut (2013)

The stratified squamous epithelium of the oesophageal mucosa usually forms a tight protective barrier against noxious components of gastro-oesophageal reflux (such as acid and bile acids), a necessary function since the distal oesophageal mucosa is exposed to physiological reflux events, even in health.

If there is a disruption to the effectiveness of this epithelial barrier (a so-called impairment of the mucosal integrity), its protective function is likely to be compromised, resulting in reflux-induced symptoms.

Non-erosive reflux disease (NERD) is the phenotype of gastro-oesophageal reflux disease most frequently encountered in clinical practice, and may be more difficult to treat than erosive reflux disease.1 Contrary to endoscopic appearances, the oesophageal mucosa in patients with NERD is not completely normal and integrity of the mucosal barrier is impaired. This has been demonstrated by morphological and functional studies. In NERD, the basal layer of oesophageal mucosal epithelium demonstrates dilated intercellular spaces (DIS).2 This histological abnormality is not specific for NERD but is related to mucosal exposure to intraluminal acid since it resolves with successful proton pump inhibitors (PPI) therapy.3

Functional studies confirm impairment of oesophageal mucosal integrity in NERD. These studies have been performed both in vitro, in biopsies of NERD patients, and in vivo, by measuring oesophageal baseline impedance.

Measurements of trans-epithelial electrical resistance (TEER) (a measure of paracellular permeability to ions), either in tissue sections or in biopsies, are used to interrogate the oesophageal mucosal barrier function. When the mucosa is exposed to solutions containing acid and bile acids, the TEER falls and the magnitude of such reduction correlates with permeability to small molecules (such …
Pharmaceutical companies’ policies and practices regarding prospective registration of dermatology-related clinical trials
Authors: J.P. Lott, K.A. Katz
Journal: British Journal of Dermatology (2006)

Appendix S1 Survey distributed to companies. Appendix S2 Sample of cover letter sent to companies. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
New Method for Terminating Cardiac Arrhythmias
Authors: Bernard Lown
Journal: JAMA (1986)

THE ECTOPIC TACHYCARDIAS are currently treated by either vagal stimulation or drugs. The 3 most effective drugs are quinidine, procainamide hydrochloride, and the digitalis glycosides. When the ectopic mechanism drives the ventricles at rates above 160 per minute, cardiac output falls and coronary blood flow is compromised. This is most likely to occur with ventricular tachycardia which constitutes a serious cardiac emergency requiring immediate treatment. Frequently, however, the arrhythmia cannot be terminated promptly. Reversion with drugs generally involves a time-consuming biologic titration. Since it is impossible in any one patient to predict either the effective or the toxic dose, small increments of antiarrhythmic drugs are given at frequent intervals until a therapeutic end point is reached. The interval between doses is determined by the gravity of the patient's illness as well as by the rapidity of action of the particular agent. It may thus take minutes, days, or even weeks
Socioeconomic status and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study
Authors: C Bengtsson
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To study whether formal education and occupational class are associated with incidence of rheumatoid arthritis overall and with the incidence of the two major subgroups of rheumatoid arthritis—seropositive (RF+) and seronegative (RF−) disease. <b>Methods:</b> 930 cases and 1126 controls participated in a population based case–control study using incident cases of rheumatoid arthritis, carried out in Sweden during the period May 1996 to June 2001. The relative risk (RR) of developing rheumatoid arthritis with 95% confidence interval (CI) was calculated for different levels of formal education compared with university degree and for different occupational classes compared with higher non-manual employees. <b>Results:</b> Subjects without a university degree had an increased risk of rheumatoid arthritis compared with those with a university degree (RR = 1.4 (95% CI, 1.2 to 1.8)). For manual employees, assistant and intermediate non-manual employees together, the risk of developing rheumatoid arthritis was about 20% more than for non-manual employees. These increased risks were more pronounced for RF+ than for RF− rheumatoid arthritis and were mainly confined to women. Smoking could not of its own explain the observed associations between risk of rheumatoid arthritis in different socioeconomic groups in Sweden. <b>Conclusions:</b> There was an association between high socioeconomic status and lower risk of rheumatoid arthritis in a population based investigation that was representative for the Swedish population. The study shows that as yet unexplained environmental or lifestyle factors, or both, influence the risk of rheumatoid arthritis, even in the relatively egalitarian Swedish society.
Proteins of nucleotide and base excision repair pathways interact in mitochondria to protect from loss of subcutaneous fat, a hallmark of aging
Authors: York Kamenisch, Maria Fousteri, Jennifer Knoch, Anna-Katharina von Thaler, Birgit Fehrenbacher, Hiroki Kato, Thomas Becker, Martijn E.T. Dollé, Raoul Kuiper, Marc Majora, Martin Schaller, Gijsbertus T.J. van der Horst, Harry van Steeg, Martin Röcken, Doron Rapaport, Jean Krutmann, Leon H. Mullenders, Mark Berneburg
Journal: The Journal of Experimental Medicine (2010)

Defects in the DNA repair mechanism nucleotide excision repair (NER) may lead to tumors in xeroderma pigmentosum (XP) or to premature aging with loss of subcutaneous fat in Cockayne syndrome (CS). Mutations of mitochondrial (mt)DNA play a role in aging, but a link between the NER-associated CS proteins and base excision repair (BER)-associated proteins in mitochondrial aging remains enigmatic. We show functional increase of CSA and CSB inside mt and complex formation with mtDNA, mt human 8-oxoguanine glycosylase (mtOGG)-1, and mt single-stranded DNA binding protein (mtSSBP)-1 upon oxidative stress. MtDNA mutations are highly increased in cells from CS patients and in subcutaneous fat of aged Csbm/m and Csa−/− mice. Thus, the NER-proteins CSA and CSB localize to mt and directly interact with BER-associated human mitochondrial 8-oxoguanine glycosylase-1 to protect from aging- and stress-induced mtDNA mutations and apoptosis-mediated loss of subcutaneous fat, a hallmark of aging found in animal models, human progeroid syndromes like CS and in normal human aging.
New GP consortiums should cover 500 000 patients, says RCGP
Authors: A. O'Dowd
Journal: BMJ (2010)

The new GP commissioning groups (consortiums) that will take charge of most NHS money in England by 2013 should cover at least 500 000 patients each, the Royal College of General Practitioners has urged.

In a paper published on 14 September the college says that 500 000 patients in each consortium is more appropriate than the 100 000 that the government proposed in its recent health white paper, Equity and Excellence: Liberating the NHS .

In Update on Commissioning Activity the college outlines its priorities and goals and considers ways to support its GP members in delivering the proposals made in the white paper, which is currently out for consultation . 

In its update …
Bistabilities and annihilation phenomena in electrophysiological cardiac models.
Authors: M Landau, P Lorente, D Michaels, J Jalife
Journal: Circulation Research (1990)

We have investigated the oscillatory behavior of cardiac cellular elements simulated by two electrophysiological models: the van Capelle and Durrer (VCD) model and the sinoatrial node cell model of Yanagihara, Noma, and Irisawa (YNI). The VCD model behavior was examined systematically by using continuation-bifurcation analysis. Bifurcation diagrams were constructed as a function of Qit1, an intrinsic parameter of the model, which sets both maximum diastolic potential and depolarization threshold of the cell. The existence of stable high amplitude oscillations was evidenced between two Hopf bifurcation points (HB). Near each HB, a zone of bistability was detected. Close to the HB that corresponded to high values of Qit1, a high amplitude periodic stable state coexisted with a stable steady state. Close to the other HB, in a narrow range of lower Qit1 values, a relatively high amplitude periodic stable state coexisted with a low amplitude periodic stable state. There was no stable steady state in the latter bistability zone. Through the use of phase-plane representations and the determination of separatrices between the different attractor basins, we could deduce the conditions of timing, polarity, and strength needed for a pulse perturbation to send the system from one state to another and vice versa. The YNI model was analyzed by numerical simulation, and the oscillatory behavior of the sinoatrial node cell was explored while applying a depolarizing bias current of various strengths. Results were similar to those obtained from the VCD model in that there were two bistability regions for two different ranges of applied bias current. Depending on current intensity, annihilation of pacemaker activity could be achieved in both zones. However, the coexistence of two oscillatory stable states was never observed in the YNI model. From the behavioral similarities of these different models, we can conclude that bistabilities and annihilation phenomena can be found in transitional zones between quiescence and rhythmic activity.
Merkel cell polyomavirus is prevalent in a subset of small cell lung cancer: a study of 31 patients
Authors: C Andres, S Ihrler, U Puchta, M J Flaig
Journal: Thorax (2009)

Merkel cell carcinoma (MCC) and small cell lung cancer (SCLC) share quite distinct similarities such as almost undistinguishable histological presentation (fig 1a,b) and highly aggressive biological behaviour with high rates of metastasis and poor survival rates.1 2 While tobacco smoking and genetic susceptibility have been identified as risk factors for SCLC,3 4 sun exposure and immunosuppression are the main risk factors for MCC.1 In January 2008, a new virus, called Merkel cell polyomavirus (MCPyV), was desribed by Feng et al as a likely causative agent of MCC, proving monoclonal MCPyV–genome integration in 8 of 10 MCCs.5 Since then these findings have been reproduced by several groups.6 7



Figure 1 
Histological features of ( a ) Merkel cell carcinoma (MCC; H&E staining, ×400) and ( b …
Up-to-date survival estimates and historical trends of cutaneous malignant melanoma in the south-east of The Netherlands
Authors: E. de Vries, S. Houterman, M.L.G. Janssen-Heijnen, T. Nijsten, S.A.M. van de Schans, A.M.M. Eggermont, J.W.W. Coebergh
Journal: Annals of Oncology (2007)
Effect of ischemia and reperfusion on cardiac ryanodine receptors--sarcoplasmic reticulum Ca2+ channels.
Authors: R Zucchi, S Ronca-Testoni, G Yu, P Galbani, G Ronca, M Mariani
Journal: Circulation Research (1994)

We investigated the effect of ischemia and reperfusion on the cardiac ryanodine receptor, which corresponds to the sarcoplasmic reticulum Ca2+ channel. Isolated working rat hearts were subjected to 10 to 30 minutes of global ischemia, followed or not by reperfusion. Ischemia produced significant reduction in the density of high-affinity 3H-ryanodine binding sites, determined either in whole-heart homogenate (Bmax, 220 +/- 22, 203 +/- 12, and 228 +/- 14 fmol/mg protein after 10, 20, and 30 minutes of ischemia versus 298 +/- 18 fmol/mg protein in the control condition; P < .01) or in a fraction enriched in sarcoplasmic reticulum (Bmax, 1.08 +/- 0.15 pmol/mg protein after 20 minutes of ischemia versus 1.69 +/- 0.08 pmol/mg protein in the control condition; P < .01). The Kd (1.5 +/- 0.1 nmol/L) and the Ca2+ dependence of high-affinity 3H-ryanodine binding were not affected by ischemia. The density of low-affinity 3H-ryanodine binding sites was also reduced after 20 minutes of ischemia (14.0 +/- 2.3 versus 34.0 +/- 8.2 pmol/mg protein in the sarcoplasmic reticulum fraction, P < .05), without significant changes in Kd (4.7 +/- 1.2 versus 2.4 +/- 1.0 mumol/L). All these changes persisted after 20 minutes of reperfusion. Analysis of tissue fractions showed that 55% of the ryanodine binding sites were retained in the pellet of a low-speed centrifugation ("nuclear pellet") and that the effects of ischemia concerned only the receptors released in the supernatant ("postnuclear supernatant"). In parallel experiments, we evaluated the effect of ryanodine on oxalate-supported Ca2+ uptake, which represents sarcoplasmic reticulum Ca2+ uptake. As expected, we found that high concentrations of ryanodine stimulated Ca2+ uptake, owing to channel blockade. The response to 900 mumol/L ryanodine was slightly reduced in crude homogenate and significantly reduced in postnuclear supernatant obtained from ischemic hearts. In conclusion, the number of ryanodine receptors is reduced after ischemia; this effect concerns a subpopulation of the receptors, persists after reperfusion, and might contribute to modify sarcoplasmic reticulum function.
Multiple Molecular Markers as Predictors of Colorectal Cancer in Patients with Normal Perioperative Serum Carcinoembryonic Antigen Levels
Authors: Jaw-Yuan Wang, Shiu-Ru Lin, Deng-Chyang Wu, Chien-Yu Lu, Fang-Jung Yu, Jan-Sing Hsieh, Tian-Lu Cheng, Lok-Beng Koay, Yih-Huei Uen
Journal: Clinical Cancer Research (2007)

In this study, a high-sensitivity colorimetric membrane array method was used to detect circulating tumor cells (CTC) in the peripheral blood of colorectal cancer (CRC) patients with normal perioperative serum carcinoembryonic antigen (CEA) levels. This membrane array method was evaluated as a potential diagnostic and postoperative surveillance tool.Membrane arrays consisting of a panel of mRNA markers that include human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and CEA mRNA were used to detect CTCs in the peripheral blood of 157 postoperative CRC patients with normal perioperative serum CEA levels and in 80 healthy individuals. Digoxigenin-labeled cDNA were amplified by reverse transcription-PCR from the peripheral blood samples, which were then hybridized to the membrane array. The sensitivity, specificity, and accuracy of membrane arrays for the detection of CTCs were then calculated.Using the four markers in combination, expression of any three markers or all the four markers in this panel was significantly correlated with the clinicopathologic characteristics, including depth of tumor invasion, lymph node metastasis, tumor-node-metastasis stage, and postoperative relapse (all P < 0.05). The interval between the detection of all four positive molecular markers and subsequent elevated CEA ranged from 3 to 8 months (median 6 months). The expression of all four mRNA markers was an independent predictor for postoperative relapse. CRC patients with all four mRNA markers expression showed a significantly poorer survival rate than those with less than four positive markers.The constructed membrane array method was helpful in the early prediction of postoperative relapse in CRC patients with normal perioperative serum CEA levels.