tbuckley/cabot-search huggingface dataset:
Abstract 5158: Plastic tumor cells engaged in vasculogenic mimicry produce PDGF-B and attract structural support
Authors: Yvette WJ Paulis, Joost J. van den Oord, Vivianne CG Tjan-Heijnen, Arjan W. Griffioen
Journal: Cancer Research (2011)

Abstract In developmental angiogenesis, pericytes are recruited by PDGF-B-expressing endothelial cells to remodel, stabilize and support the immature blood vessel. In a process called vasculogenic mimicry (VM) highly aggressive tumor cells gain the unique ability to dedifferentiate into multiple cellular phenotypes, and obtain endothelial-like characteristics. This process can lead to the formation of vasculogenic-like matrix-embedded networks, i.e. vascular-like structures, contributing to circulation. The presence of VM is associated with increased tumor malignancy. Interestingly, also the expression of PDGF in tumor cells has been demonstrated to be associated with an increased grade of malignancy. As plastic, highly aggressive tumor cells form vasculogenic-like structures resembling immature vessels, we hypothesize that plastic tumor cells engaged in VM also functionally resemble endothelial cells by seeking structural support. We demonstrate that plastic, aggressive melanoma cells transcribe and secrete PDGF-B, while in poorly aggressive melanoma cells, PDGF-B is absent. Myofibroblasts, acquired from the human vena saphena, cultured in the presence of plastic tumor cell conditioned medium display an activated phenotype. Additionally, in vitro analysis of 3D-culture on Matrigel demonstrated the functional contribution of myofibroblasts to plastic tumor cells as they structurally support the VM-characteristic networks formed. Immunohistochemical analysis of a series of cutaneous melanoma tissues showed a gradient PDGF-B staining towards the outer surface of the nest structures, i.e. the tumor cells aligning the VM-characteristic matrix networks. Consistent with the above described data, we observed staining for alpha-smooth muscle actin (α-SMA), a pericyte-specific marker, within the VM-characteristic matrix networks, thereby revealing the presence of pericytes inside these networks. Together our results demonstrate that highly aggressive, VM-positive tumor cells do not solely resemble endothelial cells phenotypically, but also actively behave like endothelial cells by producing PDGF-B and attracting structural support to their immature structures. The current findings suggest that targeting of pericytes may have an unexpected anti-tumor activity through affecting vasculogenic mimicry. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5158. doi:10.1158/1538-7445.AM2011-5158
Functional differences between hepatocytes and biliary epithelial cells in handling polymeric immunoglobulin A2 in humans, rats, and guinea pigs
Authors: S Sakisaka
Journal: Hepatology (1996)

Immunoglobulin A (IgA) in bile plays an important role in preventing the biliary tract from infection. In the present study, to clarify the functional differences between hepatocytes and biliary epithelial cells (BEC) in handling polymeric IgA2 (pIgA2), the major and important IgA in bile, we have determined in different species the binding characteristics of 125I-labeled pIgA2 to tissue sections of human, rat, and guinea pig livers. We have also examined the binding and transport features of 125I-labeled and gold-labeled pIgA2 in cultured hepatocytes and cultured BEC of rat and guinea pig. Asialofetuin, an asialoglycoprotein, or an antisecretory component antibody was used for determining the binding characteristics of pIgA2 to the cells. Grains of 125I-pIgA2 were morphometrically analyzed. In tissue sections, 125I-pIgA2 was predominantly bound to rat hepatocytes as well as to human and guinea pig BEC. The binding of 125I-pIgA2 to the cells was significantly inhibited by pretreatment with an antisecretory component (SC) antibody (P < .001), but not by preloaded asialofetuin. In cultured cells, labeled pIgA2 was observed binding predominantly to rat hepatocytes and guinea pig BEC as compared with rat BEC and guinea pig hepatocytes (both P < .001), respectively, and gold particles of gold-labeled pIgA2 were localized in the tubulovesicular structures and biliary luminal spaces of those cells. These results suggested that pIgA2 was bound selectively to hepatocytes in the rat liver, and to BEC in the human and guinea pig livers, through the SC but not through an asialoglycoprotein receptor, and was transported transcellularly and secreted into bile.
Partner and sister ask High Court for permission to let "minimally aware" woman die
Authors: C. Dyer
Journal: BMJ (2011)

The family and the former partner of a woman in a “minimally aware” state are asking the High Court in London to rule that she should have artificial feeding withdrawn and be allowed to die.

Her older sister said the 51 year old woman, named only as M, would prefer death to being permanently dependent on others for her care.

The case is the first in which the court has been asked to allow artificial nutrition and hydration to be discontinued where the patient is …
Linkage of a membrane skeleton to integral membrane glycoproteins in human platelets. Identification of one of the glycoproteins as glycoprotein Ib.
Authors: J E Fox
Journal: Journal of Clinical Investigation (1985)

Experiments were performed to determine whether platelets contain a membrane skeleton. Platelets were labeled by a sodium periodate/sodium [3H]borohydride method and lysed with Triton X-100. Much of the filamentous actin could be sedimented at low g forces (15,600 g, 4 min), but some of the actin filaments required high-speed centrifugation for their sedimentation (100,000 g, 3 h). The latter filaments differed from those in the low-speed pellet in that they could not be depolymerized by Ca2+ and could not be sedimented at low g forces even from Triton X-100 lysates of platelets that had been activated with thrombin. Actin-binding protein sedimented with both types of filaments, but 3H-labeled membrane glycoproteins were recovered mainly with the high-speed filaments. The primary 3H-labeled glycoprotein recovered with this "membrane skeleton" was glycoprotein (GP) Ib. Approximately 70% of the platelet GP Ib was present in this skeleton. Several other minor glycoproteins, including greater than 50% of the GP Ia and small amounts of three unidentified glycoproteins of Mr greater than 200,000, were also recovered with the membrane skeleton. The Triton X-100 insolubility of GP Ib, GP Ia, a minor membrane glycoprotein of 250,000 Mr, and actin-binding protein resulted from their association with actin filaments as they were rendered Triton X-100-soluble when actin filaments were depolymerized with deoxyribonuclease I and co-isolated with actin filaments on sucrose gradients. When isolated platelet plasma membranes were extracted with Triton X-100, actin, actin-binding protein, and GP Ib were recovered as the Triton X-100 residue. These studies show that unstimulated platelets contain a membrane skeleton composed of actin filaments and actin-binding protein that is distinct from the rest of the cytoskeleton and is attached to GP Ib, GP Ia, and a minor glycoprotein of 250,000 Mr on the plasma membrane.
Wedding Ring Dermatitis
Authors: Bernadine Z. Paulshock
Journal: JAMA (1969)

To the Editor:—  The most common cause of wedding ring dermatitis ( 206 :2526, 1968) has not been discussed in your letters column along with the more esoteric, radioactive, and psychoanalytical theories. Together with the privileges of the plain gold band go the responsibility of the breakfast, lunch, and supper dishes; the most common cause of wedding ring dermatitis is dishpan detergent trapped beneath the band, which is apt to tighten, abetted by the usual increase of weight which happens after marriage and which, distributed from head to toes, includes the ring finger.  Any woman could have told you gentlemen this.
Healing of rickets with phosphate supplementation in the hypophosphatemic male mouse.
Authors: P J Marie, R Travers, F H Glorieux
Journal: Journal of Clinical Investigation (1981)

The hypophosphatemic male mouse, an animal model for human vitamin D-resistant rickets, is characterized by low serum phosphorus concentration due to increased urinary phosphate excretion, rickets, osteomalacia, and dwarfism. Because phosphate administration can heal rickets but not osteomalacia in the human disease, we have compared the effect of phosphate supplementation on the epiphyseal and endosteal bone mineralization in the mutant animal. Phosphate was given in drinking water for 137 d and the biochemical and bone responses were assessed by analytical and histomorphometric methods. Treatment with phosphate normalized the endochondral calcification (vertebral growthplate thickness: 83 +/- 5 SD vs. controls [+/Y] 73 +/- 8 micrometers, NS), but did not correct the endosteal bone mineralization (mineralization front: 13.6 +/- 2.7 vs. +/Y 67.1 +/- 6.9% osteoid surface, P less than 0.001, endosteal mean osteoid seam thickness: 46.4 +/- 6.1 vs. +/Y 3.3 +/- 0.3 micrometers, P less than 0.001). In addition, both osteoblastic and osteoclastic recruitment and activity were stimulated, as a result of a probable increase in parathyroid hormone secretion following the phosphate induced fall in serum calcium. Our results show that in the hypophosphatemic mouse, phosphate supplementation can heal the epiphyseal, but not the endosteal defective bone mineralization. Then, the biochemical and skeletal response to phosphate therapy appear to be similar to what we have observed in the human disease, further stressing the interest of the animal model.
205 HIGH FREQUENCY OF ANTI-CARDIOLIPIN AND ANTIBETA2 - GLYCOPROTEIN-I POSITIVITY IN PAEDIATRIC LIVER TRANSPLANT RECIPIENTS DEVELOPING VASCULAR COMPLICATIONS
Authors: N. Hadzic, E.T. Davies, M. Hussain, J. Kostaliva, M. Rela, N.D. Heaton, D. Vergani, G. Mieli-Vergani
Journal: Journal of Hepatology (2008)
Prediction of treatment outcome in patients with chronic hepatitis C: Significance of baseline parameters and viral dynamics during therapy
Authors: Thomas Berg, Christoph Sarrazin, Eva Herrmann, Holger Hinrichsen, Tilman Gerlach, Reinhart Zachoval, Bertram Wiedenmann, Uwe Hopf, Stefan Zeuzem
Journal: Hepatology (2003)

In patients with chronic hepatitis C virus (HCV) infection scheduled for a 48-week treatment period, premature discontinuation of treatment was previously recommended if HCV-RNA levels remained detectable at week 24 of therapy. Considering the number of side effects and treatment costs, measurement of initial viral decline during therapy may identify virologic nonresponse earlier than 24 weeks. We retrospectively analyzed 260 European patients treated with standard or pegylated interferon alfa (IFN-alpha) and ribavirin for 24 to 48 weeks. Early prediction of virologic response by HCV-RNA decline at weeks 4 and 12 (Versant Quantitative [branched DNA (bDNA) 3.0]; Bayer Diagnostics, Emeryville, CA; and Qualitative [transcription-mediated amplification (TMA)] HCV RNA assay; Bayer Diagnostics) as well as clinical, biochemical, virologic, and histologic baseline parameters were analyzed by logistic regression and receiver operating characteristic (ROC) curves. A viral load at treatment week 4 above 450,000 IU/mL and at week 12 above 30,000 IU/mL was 100% predictive for virologic nonresponse in all patients. From multivariate logistic regression analysis of all patients, independent predictors for sustained virologic response were: genotypes 2 and 3 (P <.0001), a low baseline gamma-glutamyltransferase (GGT) level (P <.0001), a high baseline alanine aminotransferase level (P =.002), and a low baseline viral load (P =.04). None of the latter 3 factors were predictive for sustained virologic response when analysis was restricted to the subgroup of genotypes 2- and 3-infected patients. In conclusion, virologic nonresponse can be predicted early at week 12 of treatment independent from the applied therapeutic regimen based on a cutoff level for HCV RNA of 30,000 IU/mL. This algorithm recognizes 53.7% of nonresponders previously identified at week 24 of treatment.
Corticotrophin and tetracosactrin depot–self-administered for the treatment of eczema
Authors: D.D. MUNRO
Journal: British Journal of Dermatology (1976)

The prolonged use of self-administered corticotrophin in the form of 'CMC ACTH' (Crookes) or 'Synacthen Depot' (Ciba) has been considered in twenty-seven patients with severe subactute of chronic eczema. Complications were not troublesome and the therapeutic response was good. Many of the patients were able to control their disease fully without the effort and discomfort of additional local treatment and patients' acceptance of the treatment was high.
Abstract 3156: Autocrine signaling through release of ATP and activation of P2X7 receptor promotes migration of human lung cancer cells
Authors: Erina Takai, Mitsutoshi Tsukimoto, Hitoshi Harada, Miki Hiasa, Yoshinori Moriyama, Shuji Kojima
Journal: Cancer Research (2014)

Abstract Cell migration is essential step of cancer metastasis. TGF-β1 plays a key role in cancer progression through induction of various biological effects, including cell migration. Extracellular nucleotides, such as ATP, released from cells play a role in signaling through activation of P2 receptors. However, it remains poorly understood whether ATP-P2 receptor signaling is involved in cancer progression. We show here that release of ATP followed by activation of P2X7 receptors plays a key role in migration of lung cancer cells. Treatment with TGF-β1 facilitated migration of human lung cancer A549 cells, which was blocked by pretreatment with ecto-nucleotidase and P2 receptor antagonists in a wound healing-based assay and Transwell assay. ATP and P2 agonists facilitated cell migration. TGF-β1-induced actin remodeling, which contributes to cell migration, was also suppressed by pretreatment with ecto-nucleotidase and P2 receptor antagonists. Knockdown of P2X7 receptor suppressed TGF-β1-induced migration and actin remodeling. These results indicate the involvement of TGF-β1-induced ATP release in cancer cell migration, at least in part, through activation of P2X7 receptors. We found that TGF-β1 caused release of ATP from A549 cells within 10 minutes. Both ATP-enriched vesicles and expression of a vesicular nucleotide transporter (VNUT) SLC17A9, which is responsible for exocytosis of ATP, were found in cytosol of A549 cells. TGF-β1 failed to induce release of ATP from SLC17A9-knockdown cells. TGF-β1-induced cell migration and actin remodeling were also decreased in SLC17A9-knockdown cells. These results suggest the importance of exocytosis of ATP in cell migration. In addition, treatment with specific antagonist of P2X7 receptor (A438079) suppressed TGF-β1-induced migration of another human lung cancer H292 cells, but not of non-cancerous BEAS-2B cells. H292 cells released ATP in response to TGF-β1 stimulation, while BEAS-2B cells did not. Furthermore, in high-motile human lung cancer PC-9 cells, a large amount of ATP was released under standard cell culture condition, and P2X7 receptor was constitutively activated. Blockade of P2X7 receptor significantly suppressed motile activity of PC-9 cells. Taken together, these results suggest that autocrine signaling through release of ATP and activation of P2X7 receptor play a role in migration of human lung cancer cells. Citation Format: Erina Takai, Mitsutoshi Tsukimoto, Hitoshi Harada, Miki Hiasa, Yoshinori Moriyama, Shuji Kojima. Autocrine signaling through release of ATP and activation of P2X7 receptor promotes migration of human lung cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3156. doi:10.1158/1538-7445.AM2014-3156
Air Pollution
Authors: Rolf Eliassen
Journal: New England Journal of Medicine (1962)

AIR pollution from man-made sources is not new — it has been present for a long time, as witness the words that Shakespeare put into the mouth of Hamlet: "This most excellent canopy, the air — why it appears no other thing to me than a foul and pestilent congregation of vapours." Since World War II the problem has become more intense as a result of the vast population gains in urban areas, with the attending growth in number of motor vehicles and the usage of fuel for these, for power plants, for industries and increased domestic and commercial activities. . . .
RADical Response Puts an Exceptional Responder in CHKmate: A Synthetic Lethal Curative Response to DNA-Damaging Chemotherapy?
Authors: Guang Peng, Scott E. Woodman, Gordon B. Mills
Journal: Cancer Discovery (2014)

Abstract Summary: In this issue of Cancer Discovery, AI-Ahmadie and colleagues identify a somatic mutation in the RAD50 gene as a likely contributing factor to an unusual curative response to systemic combination therapy employing the DNA-damaging agent irinotecan and a checkpoint kinase 1 inhibitor in a patient with recurrent, metastatic small-cell cancer. This study highlights the importance of in-depth analysis of exceptional responders to chemotherapy and targeted therapy in early-phase clinical trials and opens new avenues for developing cancer genome–based combination therapy to improve the efficacy of traditional chemotherapy through synthetically lethal interactions. Cancer Discov; 4(9); 988–90. ©2014 AACR. See related article by AI-Ahmadie et al., p. 1014
Treatment of patients with systemic sclerosis with extracorporeal photochemotherapy (photopheresis)
Authors: Dory N.H. Enomoto, Jan R. Mekkes, Patrick M.M. Bossuyt, Si-La Yongd, Theo A. Outd, Rick Hoekzema, Menno A. de Rie, Peter T.A. Schellekens, Ineke J.M. ten Berge, Corianne A.J.M. de Borgieb, Jan D. Bos
Journal: Journal of the American Academy of Dermatology (1999)
Life threatening injuries to the chest caused by plastic bullets.
Authors: A J Ritchie, J R Gibbons
Journal: BMJ (1990)

Plastic bullets have been available to police forces in the United Kingdom since 1988' but have been used to control public disorder and riots in Northern Ireland since 1975.They were intended to be more accurate and no more damaging than the rubber bullet that they replaced.2They are unique in that they are fired to inflict non-penetrating blunt trauma in an effort to immobilise rather than kill.Over 54 000 rounds were fired during the 13 years of this study from 1975.In this time 80 patients presented to hospitals in Belfast with injuries to the chest caused by plastic bullets.We assessed the outcome of these injuries.
Calcium supplementation and postmenopausal bone loss.
Authors: L Nilas, C Christiansen, P Rodbro
Journal: BMJ (1984)

A series of 103 early postmenopausal women completed a questionnaire about their dietary calcium intake and were then divided into three groups: those with an intake below 550 mg/day, those with an intake between 550 and 1150 mg/day, and those with an intake above 1150 mg/day. Thereafter they were given a daily supplement of 500 mg calcium for two years and had their bone mineral content measured every three months. Any changes found were taken as an estimate of bone calcium balance. All three groups showed a similar fall in bone mineral content over the two years, indicating that a calcium intake of 1000-2000 g daily is ineffective in preventing bone loss in the early menopause.
Tests of Association
Authors: Sidney Shindell
Journal: JAMA (1963)

WHEN A PHYSICIAN examines a patient, he makes a series of observations. He then relates these observations to a body of existing knowledge and attempts to reason from the relationship. When an investigator attacks a problem, he employs essentially the same mental processes. He, too, makes a series of observations; relates these to each other, using a body of knowledge with which he examines the relationships; and attempts to reason from the result.  In the simplest form of study a single observation is made on a single subject. Illustrative of this type of study is the performance of a white blood cell (WBC) count on a measured amount of blood of an individual. The clinician automatically compares the WBC's of his particular patient to the existing body of knowledge and makes his judgment of the significance of the count accordingly. As a profession, we have a fairly clear idea as
Glucose-6-Phosphate Dehydrogenase Deficiency in Sickle-Cell Disease
Authors: FRED J. OELSHLEGEL
Journal: Annals of Internal Medicine (1974)

Comments and Corrections1 September 1974Glucose-6-Phosphate Dehydrogenase Deficiency in Sickle-Cell DiseaseFRED J. OELSHLEGEL JR., PH.D.FRED J. OELSHLEGEL JR., PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-3-413 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I read with interest the article, "Glucose-6-Phosphate Dehydrogenase Deficiency in Sickle-Cell Anemia," by Steinberg and Dreiling (Ann Intern Med80:217-220 1974). Among their patients with sickle-cell disease they could not find the increased prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency previously reported by others, most recently Piomelli and associates (1). Steinberg and Dreiling very nicely list the possible reasons for their negative findings. It may turn out that in some populations there is a significantly higher prevalence of G6PD deficiency. For such populations the speculation that the concurrent presence of G6PD deficiency somehow tempers the effects of...References References1. PIOMELLIREINDORFARZANIAN SCM: Clinical and biochemical interactions of glucose-6-phosphate dehydrogenase activity and sickle cell anemia. N Engl J Med 287:213-217, 1972 CrossrefMedlineGoogle Scholar2. PETRAKISWIESENFELDSAMS NSB: Prevalence of sickle-cell trait and glucose-6-phosphate dehydrogenase deficiency. N Engl J Med 282:767-770, 1970 CrossrefMedlineGoogle Scholar3. SINISCALCOBERNINIFILLIPPI MLG: Population genetics of hemoglobin variants, thalassemia and glucose-6-phosphate dehydrogenase deficiency with particular reference to the malaria hypothesis. Bull WHO 34:379-393, 1966 MedlineGoogle Scholar1. LUZZATOUSANGAREDDY LES: Glucose-6-phosphate dehydrogenase deficient red cells: resistance to infection by malarial parasites. Science 164:839-842, 1962 CrossrefGoogle Scholar2. BEUTLERJOHNSONPOWARS ECD: Prevalence of glucose-6-phosphate dehydrogenase deficiency in sickle-cell disease. N Engl J Med 290:826-828, 1974 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Human Genetics University of Michigan Medical School Ann Arbor, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1974Volume 81, Issue 3Page: 413-414KeywordsAnemiaDehydrogenasesGlucose-6-phosphate dehydrogenase deficiencyPopulation statistics Issue Published: 1 September 1974 PDF downloadLoading ...