tbuckley/cabot-search huggingface dataset:
Multifunctional Roles for Serum Protein Fetuin-A in Inhibition of Human Vascular Smooth Muscle Cell Calcification
Authors: Joanne L. Reynolds, Jeremy N. Skepper, Rosamund McNair, Takeshi Kasama, Kunal Gupta, Peter L. Weissberg, Willi Jahnen-Dechent, Catherine M. Shanahan
Journal: Journal of the American Society of Nephrology (2005)

Vascular calcification predicts an increased risk for cardiovascular events/mortality in atherosclerosis, diabetes, and ESRD. Serum concentrations of alpha(2)-Heremens-Schmid glycoprotein, commonly referred to as fetuin-A, are reduced in ESRD, a condition associated with an elevated circulating calcium x phosphate product. Mice that lack fetuin-A exhibit extensive soft tissue calcification, which is accelerated on a mineral-rich diet, suggesting that fetuin-A acts to inhibit calcification systemically. Western blot and immunohistochemistry demonstrated that serum-derived fetuin-A co-localized with calcified human vascular smooth muscle cells (VSMC) in vitro and in calcified arteries in vivo. Fetuin-A inhibited in vitro VSMC calcification, induced by elevated concentrations of extracellular mineral ions, in a concentration-dependent manner. This was achieved in part through inhibition of apoptosis and caspase cleavage. Confocal microscopy and electron microscopy-immunogold demonstrated that fetuin-A was internalized by VSMC and concentrated in intracellular vesicles. Subsequently, fetuin-A was secreted via vesicle release from apoptotic and viable VSMC. Vesicles have previously been identified as the nidus for mineral nucleation. The presence of fetuin-A in vesicles abrogated their ability to nucleate basic calcium phosphate. In addition, fetuin-A enhanced phagocytosis of vesicles by VSMC. These observations provide evidence that the uptake of the serum protein fetuin-A by VSMC is a key event in the inhibition of vesicle-mediated VSMC calcification. Strategies aimed at maintaining normal circulating levels of fetuin-A may prove beneficial in patients with ESRD.
Clinical Benefit of a Gluten-Free Diet in Type 1 Diabetic Children With Screening-Detected Celiac Disease
Authors: Dorte Hansen, Bendt Brock-Jacobsen, Elisabeth Lund, Christina Bjørn, Lars P. Hansen, Christian Nielsen, Claus Fenger, Søren T. Lillevang, Steffen Husby
Journal: Diabetes Care (2006)

This study was performed to 1) determine the prevalence of celiac disease in Danish children with type 1 diabetes and 2) estimate the clinical effects of a gluten-free diet (GFD) in patients with diabetes and celiac disease.In a region comprising 24% of the Danish population, all patients <16 years old with type 1 diabetes were identified and 269 (89%) were included in the study. The diagnosis of celiac disease was suspected in patients with endomysium and tissue transglutaminase antibodies in serum and confirmed by intestinal biopsy. Patients with celiac disease were followed for 2 years while consuming a GFD.In 28 of 33 patients with celiac antibodies, an intestinal biopsy showed villous atrophy. In 5 patients, celiac disease had been diagnosed previously, giving an overall prevalence of 12.3% (95% CI 8.6-16.9). Patients with celiac disease had a lower SD score (SDS) for height (P < 0.001) and weight (P = 0.002) than patients without celiac disease and were significantly younger at diabetes onset (P = 0.041). A GFD was obtained in 31 of 33 patients. After 2 years of follow-up, there was an increase in weight SDS (P = 0.006) and in children <14 years old an increase in height SDS (P = 0.036). An increase in hemoglobin (P = 0.002) and serum ferritin (P = 0.020) was found, whereas HbA(1c) remained unchanged (P = 0.311) during follow-up.This population-based study showed the highest reported prevalence of celiac disease in type 1 diabetes in Europe. Patients with celiac disease showed clinical improvements with a GFD. We recommend screening for celiac disease in all children with type 1 diabetes.
Liver Kupffer cells rapidly remove red blood cell–derived vesicles from the circulation by scavenger receptors
Authors: Frans L. A. Willekens, Jan M. Werre, J. Kar Kruijt, Bregt Roerdinkholder-Stoelwinder, Yvonne A. M. Groenen-Döpp, Annegeet G. van den Bos, Giel J. C. G. M. Bosman, Theo J. C. van Berkel
Journal: Blood (2004)
In vitro growth rate of placental fibroblasts is developmentally regulated.
Authors: M E Fant
Journal: Journal of Clinical Investigation (1991)

Placental cells of mesenchymal origin were used to study the regulation of fetal growth at the cellular level. A significant difference in the in vitro growth rates of placental fibroblasts was observed as a function of gestational age. Cells derived from 10-19-wk placentae exhibited proliferative rates two to three times greater than cells derived from 7-9-wk placentae (16-30 h vs. 30-60 h, P less than 0.001). The proliferation rate remained stable throughout multiple passages in culture. Additionally, these two groups of cell strains exhibited marked differences in their responsiveness to mitogenic stimuli. Using maximal effective concentrations, insulin-like growth factor I interacted synergistically with epidermal growth factor and fibroblast growth factor to stimulate DNA synthesis in cells derived from 10-19-wk placentae. By contrast, the interaction of insulin-like growth factor 1 with epidermal growth factor and fibroblast growth factor exhibited significantly less synergy in 7-9-wk cells. These findings argue that the accelerated growth rate of human fetal cells results primarily from developmental events intrinsic to the cells and is associated with enhanced responsiveness to the mitogenic action of peptide growth factors.
Risk of Non-Melanoma Cancers in First-Degree Relatives of CDKN2A Mutation Carriers
Authors: Bhramar Mukherjee, John Oliver DeLancey, Leon Raskin, Jessica Everett, Joanne Jeter, Colin B. Begg, Irene Orlow, Marianne Berwick, Bruce K. Armstrong, Anne Kricker, Loraine D. Marrett, Robert C. Millikan, Hoda Anton Culver, Stefano Rosso, Roberto Zanetti, Peter A. Kanetsky, Lynn From, Stephen B. Gruber
Journal: JNCI Journal of the National Cancer Institute (2012)

The purpose of this study was to quantify the risk of cancers other than melanoma among family members of CDKN2A mutation carriers using data from the Genes, Environment and Melanoma study. Relative risks (RRs) of all non-melanoma cancers among first-degree relatives (FDRs) of melanoma patients with CDKN2A mutations (n = 65) and FDRs of melanoma patients without mutations (n = 3537) were calculated as the ratio of estimated event rates (number of cancers/total person-years) in FDRs of carriers vs noncarriers with exact Clopper-Pearson-type tests and 95% confidence intervals (CIs). All statistical tests were two-sided. There were 56 (13.1%) non-melanoma cancers reported among 429 FDRs of mutation carriers and 2199 (9.4%) non-melanoma cancers in 23 452 FDRs of noncarriers. The FDRs of carriers had an increased risk of any cancer other than melanoma (56 cancers among 429 FDRs of carrier probands vs 2199 cancers among 23 452 FDRs of noncarrier probands; RR = 1.5, 95% CI = 1.2 to 2.0, P = .005), gastrointestinal cancer (20 cancers among 429 FDRs of carrier probands vs 506 cancers among 23 452 FDRs of noncarrier probands; RR = 2.4, 95% CI = 1.4 to 3.7, P = .001), and pancreatic cancer (five cancers among 429 FDRs of carrier probands vs 41 cancers among 23 452 FDRs of noncarrier probands; RR = 7.4, 95% CI = 2.3 to 18.7, P = .002). Wilms tumor was reported in two FDRs of carrier probands and three FDRs of noncarrier probands (RR = 40.4, 95% CI = 3.4 to 352.7, P = .005). The lifetime risk of any cancer other than melanoma among CDKN2A mutation carriers was estimated as 59.0% by age 85 years (95% CI = 39.0% to 75.4%) by the kin-cohort method, under the standard assumptions of Mendelian genetics on the genotype distribution of FDRs conditional on proband genotype.
The unrestricted use of paclitaxel- versus sirolimus-eluting stents for coronary artery disease in an unselected population
Authors: Andrew T.L. Ong, Patrick W. Serruys, Jiro Aoki, Angela Hoye, Carlos A.G. van Mieghem, Gaston A. Rodriguez-Granillo, Marco Valgimigli, Karel Sonnenschein, Evelyn Regar, Martin van der Ent, Peter P.T. de Jaegere, Eugene P. McFadden, Georgios Sianos, Willem J. van der Giessen, Pim J. de Feyter, Ron T. van Domburg
Journal: Journal of the American College of Cardiology (2005)
OC-092 Contralesional application of the novel brain stimulation intervention transcranial direct current stimulation (TDCS) restores brain and swallowing function in the human pharyngeal motor cortex: Abstract OC-092 Figure 1
Authors: D H Vasant, S Hamdy, E Michou, S Mistry
Journal: Gut (2012)

<h3>Introduction</h3> Recovery of swallowing function in unilateral dysphagic stroke patients is associated with increased pharyngeal motor cortex excitability of the unlesioned hemisphere. “Virtual-lesioning” the human pharyngeal motor cortex transiently disrupts swallowing neurophysiological and behavioural function for up to 45 min. During this window of opportunity we trialled the effects of contralesional tDCS, a novel non-invasive brain stimulation technology, on “virtual-lesion” induced brain and behavioural changes to swallowing function. <h3>Methods</h3> In 15 healthy volunteers (eight males, 21–61 years old) hemispheric lateralisation and cortical excitability of pharyngeal and hand motor cortex were mapped using Transcranial Magnetic Stimulation via an intraluminal catheter with electromyography and pressure sensors. Volunteers then received a “virtual-lesion” to the strongest pharyngeal projection and were randomised to either 10 min of 1.5mA Anodal tDCS (Active) or Sham to the unlesioned hemisphere on separate days. In <i>Experiment 1</i>, effects of tDCS on cortical excitability were compared to baseline over 60 min. In <i>Experiment</i> 2, swallowing behavioural measurements using a swallowing reaction time task were used to calculate a time window for challenge swallows. Swallowing behaviour was assessed for 60 min after tDCS and compared to baseline. Data were compared using repeated measures ANOVA. <h3>Results</h3> <i>Experiment 1;</i> compared to sham, active tDCS abolished the inhibitory effects of the “virtual-lesion” bilaterally (p=0.017) with a maximum increase in excitability from baseline of 34% in the un-lesioned hemisphere (Abstract OC-092 figure 1). No significant changes were observed in the hand. <i>Experiment 2;</i> compared to sham, active tDCS significantly improved challenge swallow performance (p=0.025) with a maximal improvement of 174%. <h3>Conclusion</h3> Contralesional tDCS reverses the neurophysiological and behavioural consequences of a “virtual-lesion” in healthy individuals and has therapeutic potential for dysphagia rehabilitation. <h3>Competing interests</h3> None declared.
Treatment of diffuse in-stent restenosis with rotational atherectomy followed by radiation therapy with a rhenium-188–mercaptoacetyltriglycine-filled balloon
Authors: Seong-Wook Park, Myeong-Ki Hong, Dae Hyuk Moon, Seung Jun Oh, Cheol Whan Lee, Jae-Joong Kim, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2001)
2016 LONG-TERM OUTCOMES FOLLOWING COMBINATION TREATMENT WITH BOCEPREVIR PLUS PEG-INTRON/RIBAVIRIN (P/R) IN PATIENTS WITH CHRONIC HEPATITIS C, GENOTYPE 1 (CHC-G1)
Authors: J.M. Vierling, R. Ralston, E.J. Lawitz, J. McCone, S. Gordon, D. Pound, M. Davis, J. Galati, I. Jacobson, L. Rossaro, F.H. Anderson, J. King, W. Cassidy, M. Bourliere, R. Esteban-Mur, N. Ravendhran, G. Galler, P. Mendez, C.A. Brass, J.K. Albrecht
Journal: Journal of Hepatology (2010)
Unacceptably High Mortality Related to Measles Epidemics in Niger, Nigeria, and Chad
Authors: R. F Grais, C Dubray, S Gerstl, J. P Guthmann, A Djibo, K. D Nargaye, J Coker, K. P Alberti, A Cochet, C Ihekweazu, N Nathan, L Payne, K Porten, D Sauvageot, B Schimmer, F Fermon, M. E Burny, B. S Hersh, P. J Guerin
Journal: PLoS Medicine (2006)

Background Despite the comprehensive World Health Organization (WHO)/United Nations Children's Fund (UNICEF) measles mortality–reduction strategy and the Measles Initiative, a partnership of international organizations supporting measles mortality reduction in Africa, certain high-burden countries continue to face recurrent epidemics. To our knowledge, few recent studies have documented measles mortality in sub-Saharan Africa. The objective of our study was to investigate measles mortality in three recent epidemics in Niamey (Niger), N'Djamena (Chad), and Adamawa State (Nigeria). Methods and Findings We conducted three exhaustive household retrospective mortality surveys in one neighbourhood of each of the three affected areas: Boukoki, Niamey, Niger (April 2004, n = 26,795); Moursal, N'Djamena, Chad (June 2005, n = 21,812); and Dong District, Adamawa State, Nigeria (April 2005, n = 16,249), where n is the total surveyed population in each of the respective areas. Study populations included all persons resident for at least 2 wk prior to the study, a duration encompassing the measles incubation period. Heads of households provided information on measles cases, clinical outcomes up to 30 d after rash onset, and health-seeking behaviour during the epidemic. Measles cases and deaths were ascertained using standard WHO surveillance-case definitions. Our main outcome measures were measles attack rates (ARs) and case fatality ratios (CFRs) by age group, and descriptions of measles complications and health-seeking behaviour. Measles ARs were the highest in children under 5 y old (under 5 y): 17.1% in Boukoki, 17.2% in Moursal, and 24.3% in Dong District. CFRs in under 5-y-olds were 4.6%, 4.0%, and 10.8% in Boukoki, Moursal, and Dong District, respectively. In all sites, more than half of measles cases in children aged under 5 y experienced acute respiratory infection and/or diarrhoea in the 30 d following rash onset. Of measles cases, it was reported that 85.7% (979/1,142) of patients visited a health-care facility within 30 d after rash onset in Boukoki, 73.5% (519/706) in Moursal, and 52.8% (603/1,142) in Dong District. Conclusions Children in these countries still face unacceptably high mortality from a completely preventable disease. While the successes of measles mortality–reduction strategies and progress observed in measles control in other countries of the region are laudable and evident, they should not overshadow the need for intensive efforts in countries that have just begun implementation of the WHO/UNICEF comprehensive strategy.
Human<i>Streptococcus suis</i>Meningitis in the United States
Authors: Kara S. Willenburg, Deborah E. Sentochnik, Ruth N. Zadoks
Journal: New England Journal of Medicine (2006)

To the Editor: Streptococcus suis commonly causes meningitis in swine. Human infection is infrequent and is typically manifested as meningitis, frequently followed by permanent sensorineural hearing loss. Most cases have occurred in Southeast Asia. A recent outbreak in China resulted in substantial morbidity and mortality. The World Health Organization reports that nearly all those affected were farmers or butchers who had been either killing sick pigs or handling their meat. Transmission may occur through breaks in the skin.1 We report a case of human S. suis infection in the United States. A 59-year-old, previously healthy male farmer presented with a . . .
Localization of hepatocyte growth factor in human and rat tissues: An immunohistochemical study
Authors: Helmut K. Wolf, Reza Zarnegar, George K. Michalopoulos
Journal: Hepatology (1991)

Hepatocyte growth factor is a protein growth factor with a strong mitogenic effect on hepatocytes. Recently, hepatocyte growth factor and hepatocyte growth factor messenger RNA have been extracted from several organs of humans, rats and rabbits. This study was undertaken to comprehensively define and compare the cellular localization of hepatocyte growth factor in human and rat tissues in detail. Paraffin-embedded sections and frozen sections were examined by immunohistochemistry using a polyclonal antiserum to hepatocyte growth factor. The distribution of hepatocyte growth factor was almost identical in humans and rats. Strong or moderate cytoplasmic immunoreactivity for hepatocyte growth factor was present in most surface epithelia, distal tubules and collecting ducts of the kidneys, large neurons, megakaryocytes, granulocytes, exocrine pancreas, salivary glands, prostate, epididymis and trophoblast. Varying degrees of immunoreactivity were observed in endothelial cells, chondrocytes and macrophages. We conclude that hepatocyte growth factor is widely distributed in numerous tissues and cell types independent of their regenerative activity. This suggests that hepatocyte growth factor may have mitogenic and/or trophic effects on multiple cell types in addition to hepatocytes.
O<sub>2</sub>Modulates Large-Conductance Ca<sup>2+</sup>-Dependent K<sup>+</sup>Channels of Rat Chemoreceptor Cells by a Membrane-Restricted and CO-Sensitive Mechanism
Authors: A. M. Riesco-Fagundo, M. T. Pérez-García, C. González, J. R. López-López
Journal: Circulation Research (2001)

Hypoxic inhibition of large-conductance Ca(2+)-dependent K(+) channels (maxiK) of rat carotid body type I cells is a well-established fact. However, the molecular mechanisms of such inhibition and the role of these channels in the process of hypoxic transduction remain unclear. We have examined the mechanisms of interaction of O(2) with maxiK channels exploring the effect of hypoxia on maxiK currents recorded with the whole-cell and the inside-out configuration of the patch-clamp technique. Hypoxia inhibits channel activity both in whole-cell and in excised membrane patches. This effect is strongly voltage- and Ca(2+)-dependent, being maximal at low [Ca(2+)] and low membrane potential. The analysis of single-channel kinetics reveals a gating scheme comprising three open and five closed states. Hypoxia inhibits channel activity increasing the time the channel spends in the longest closed states, an effect that could be explained by a decrease in the Ca(2+) sensitivity of those closed states. Reducing maxiK channels with dithiothreitol (DTT) increases channel open probability, whereas oxidizing the channels with 2,2'-dithiopyridine (DTDP) has the opposite effect. These results suggest that hypoxic inhibition is not related with a reduction of channel thiol groups. However, CO, a competitive inhibitor of O(2) binding to hemoproteins, fully reverts hypoxic inhibition, both at the whole-cell and the single-channel level. We conclude that O(2) interaction with maxiK channels does not require cytoplasmic mediators. Such interaction could be mediated by a membrane hemoprotein that, as an O(2) sensor, would modulate channel activity.
Respiratory complications of relapsing polychondritis
Authors: G. J. Gibson, P. Davis
Journal: Thorax (1974)

<b>Gibson, G. J. and Davis, P. (1974).</b><i>Thorax</i>, <b>29</b>, 726-731. <b>Respiratory complications of relapsing polychondritis.</b> The respiratory function of a patient with relapsing polychondritis is described. He had severe airflow obstruction due to disease of both the extra and intrathoracic large airways. Evidence of small airways disease was lacking. The airflow obstruction was probably due to a combination of structural narrowing and an enhanced dynamic effect. Despite the severity of his disease the patient9s exercise capacity was only slightly reduced but he developed carbon dioxide retention on exercise. Involvement of the airways is a common feature of this rare disease and demands full physiological and radiographic assessment if tracheostomy or other surgical procedure is contemplated.
Endostatin-Cytosine Deaminase Fusion Protein Suppresses Tumor Growth by Targeting Neovascular Endothelial Cells
Authors: Fu Ou-Yang, Keng-Li Lan, Chun-Te Chen, Jaw-Ching Liu, Chu-Li Weng, Chao-Kai Chou, Xiaoming Xie, Jen-Yu Hung, Yongkun Wei, Gabriel N. Hortobagyi, Mien-Chie Hung
Journal: Cancer Research (2006)

Endostatin, an angiogenesis inhibitor tested in multiple clinical trials, selectively targets neovascular endothelial cells, suppressing tumor growth. To enhance the therapeutic efficacy of endostatin, we fused endostatin with cytosine deaminase, which converts a prodrug 5-flucytosine into a cytotoxic 5-fluorouracil. This therapeutic strategy was developed based on the observation that the endostatin-green fluorescence protein gene and endostatin-luciferase gene selectively target to endothelial cells in vitro and to the tumor site in vivo, respectively. When we used the endostatin-cytosine deaminase fusion protein to treat s.c. grafted tumors or experimental metastasis tumors, our results showed that endostatin-cytosine deaminase treatment provided stronger tumor growth suppression and increased mean survival time of the mice compared with the treatments of endostatin alone, cytosine deaminase alone, or endostatin plus cytosine deaminase. The endostatin-cytosine deaminase protein significantly inhibited the growth of endothelial cells and preferentially induced tumor cell apoptosis. This endostatin-cytosine deaminase fusion approach opens an avenue for cancer-targeting therapy.
Ablating Barrett's metaplastic epithelium: are the techniques ready for clinical use?
Authors: J J G H M Bergman
Journal: Gut (2006)

Medullary interneurons of the preBötzinger complex assemble excitatory networks that produce inspiratory-related neural rhythms, but the importance of somatodendritic conductances in rhythm generation is still incompletely understood. Synaptic input may cause Ca<sup>2+</sup> accumulation postsynaptically to evoke a Ca<sup>2+</sup>-activated inward current that contributes to inspiratory burst generation. We measured Ca<sup>2+</sup> transients by two-photon imaging dendrites while recording neuronal somata electrophysiologically. Dendritic Ca<sup>2+</sup> accumulation frequently precedes inspiratory bursts, particularly at recording sites 50–300 μm distal from the soma. Preinspiratory Ca<sup>2+</sup> transients occur in hotspots, not ubiquitously, in dendrites. Ca<sup>2+</sup> activity propagates orthodromically toward the soma (and antidromically to more distal regions of the dendrite) at rapid rates (300–700 μm/s). These high propagation rates suggest that dendritic Ca<sup>2+</sup> activates an inward current to electrotonically depolarize the soma, rather than propagate as a regenerative Ca<sup>2+</sup> wave. These data provide new evidence that respiratory rhythmogenesis may depend on dendritic burst-generating conductances activated in the context of network activity.
Cancer Cachexia Signaling Pathways Continue to Emerge Yet Much Still Points to the Proteasome
Authors: Swarnali Acharyya, Denis C. Guttridge
Journal: Clinical Cancer Research (2007)

Abstract Cachexia is a life-threatening consequence of cancer that diminishes both quality of life and survival. It is a syndrome that is characterized by extreme weight loss resulting mainly from the depletion of skeletal muscle. Research from the past decades investigating the mechanisms of tumor-induced muscle wasting has identified several key cachectic factors that act through the ubiquitin-dependent proteasome system. Signaling pathways that mediate the effects of these cachectic factors have also subsequently emerged. Here, we review some of these pathways specific to myostatin, nuclear factor κB, and the newly elucidated dystrophin glycoprotein complex. Although these molecules are likely to employ distinct modes of action, results suggest that they nevertheless maintain a link to the proteasome pathway. Therefore, although the proteasome remains a preferred choice for therapy, the continually emerging upstream signaling molecules serve as additional promising therapeutic targets for the treatment of tumor-induced muscle wasting.