tbuckley/cabot-search huggingface dataset:
Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation
Authors: Eli Vlaisavljevich, Yasemin Yuksel Durmaz, Adam Maxwell, Mohamed ElSayed, Zhen Xu
Journal: Theranostics (2013)

This paper is an initial work towards developing an image-guided, targeted ultrasound ablation technique by combining histotripsy with nanodroplets that can be selectively delivered to tumor cells.Using extremely short, high-pressure pulses, histotripsy generates a dense cloud of cavitating microbubbles that fractionates tissue.We hypothesize that synthetic nanodroplets that encapsulate a perfluoropentane (PFP) core will transition upon exposure to ultrasound pulses into gas microbubbles, which will rapidly expand and collapse resulting in disruption of cells similar to the histotripsy process but at a significantly lower acoustic pressure.The significantly reduced cavitation threshold will allow histotripsy to be selectively delivered to the tumor tissue and greatly enhance the treatment efficiency while sparing neighboring healthy tissue.To test our hypothesis, we prepared nanodroplets with an average diameter of 204±4.7 nm at 37°C by self-assembly of an amphiphilic triblock copolymer around a PFP core followed by cross-linkage of the polymer shell forming stable nanodroplets.The nanodroplets were embedded in agarose tissue phantoms containing a sheet of red blood cells (RBCs), which were exposed to 2-cycle pulses applied by a 500 kHz focused transducer.Using a high speed camera to monitor microbubble generation, the peak negative pressure threshold needed to generate bubbles >50 μm in agarose phantoms containing nanodroplets was measured to be 10.8 MPa, which is significantly lower than the 28.8 MPa observed using ultrasound pulses alone.High speed images also showed cavitation microbubbles produced from the nanodroplets displayed expansion and collapse similar to histotripsy alone at higher pressures.Nanodroplet-mediated histotripsy created consistent, well-defined fractionation of the RBCs in agarose tissue phantoms at 10 Hz pulse repetition frequency similar to the lesions generated by histotripsy alone but at a significantly lower pressure.These results support our hypothesis and demonstrate the potential of using nanodroplet-mediated histotripsy for targeted cell ablation.
Stimulation of Ca++ binding and ATPase activity of dog cardiac myofibrils by AR-L 115BS, a novel cardiotonic agent.
Authors: R J Solaro, J C Rüegg
Journal: Circulation Research (1982)

AR-L 115BS, a benzimidazole derivative, is a positive inotropic agent that has been shown to increase active tension development and unloaded shortening velocity of chemically skinned heart muscle preparations at submaximal activating levels of free Ca++. We measured the effect of AR-L on relations between free Ca++, bound Ca++ and ATPase activity of dog cardiac myofibrils. At pCa 6, 100-300 micrometers AR-L increased myofibrillar ATPase activity maximally by about 30%. The concentration of AR-L giving half-maximal activation of myofibrillar ATPase activity was about 10 micrometers, and is similar to plasma concentrations associated with elevated contractility in intact animals. There was no effect of AR-L on myofibrillar ATPase activity at pCa 5 or 8, and the relation between pCa and percent activation of myofibrillar ATPase activity was shifted to the left by 0.4-0.5 pCa units in the presence of 100 micrometers AR-L. Calcium binding by cardiac myofibrils was increased by AR-L in the presence and absence of MgATP by 0.2-0.3 nmol/mg myofibrillar protein over a broad range of free Ca++ concentrations, a result suggesting that AR-L increases the affinity of myofibrillar troponin C for Ca++. The shift in the pCa giving half maximal and myofibrillar ATPase activity induced by raising the free Mg++ from 1.0 to 10 mm was unaffected by AR-L. These results indicate that the positive actions of AR-L 115BS on cardiac contractility may involve direct activation of myofibrils by virtue of an increased affinity of thin filament receptors for Ca++.
Inhibition of Cyclooxygenase-2 Suppresses Lymph Node Metastasis via Reduction of Lymphangiogenesis
Authors: Caname Iwata, Mitsunobu R. Kano, Akiyoshi Komuro, Masako Oka, Kunihiko Kiyono, Erik Johansson, Yasuyuki Morishita, Masakazu Yashiro, Kosei Hirakawa, Michio Kaminishi, Kohei Miyazono
Journal: Cancer Research (2007)

Abstract Cyclooxygenase-2 (COX-2) inhibitor has been reported to suppress tumor progression. However, it is unclear whether this inhibitor can also prevent lymphatic metastasis. To determine the effects of COX-2 inhibitor on lymphatic metastasis, etodolac, a COX-2 inhibitor, was given p.o. to mice bearing orthotopic xenografts or with carcinomatous peritonitis induced with a highly metastatic human diffuse-type gastric carcinoma cell line, OCUM-2MLN. Tumor lymphangiogenesis was significantly decreased in etodolac-treated mice compared with control mice. Consistent with this decrease in lymphangiogenesis, the total weight of metastatic lymph nodes was less in etodolac-treated mice than in control mice. Immunohistochemical analysis revealed that the major source of vascular endothelial growth factor-C (VEGF-C) and VEGF-D was F4/80-positive macrophages in our models. The mRNA levels of VEGF-C in mouse macrophage-like RAW264.7 cells, as well as those in tumor tissues, were suppressed by etodolac. The growth of human dermal lymphatic microvascular endothelial cells was also suppressed by etodolac. Supporting these findings, etodolac also inhibited lymphangiogenesis in a model of chronic aseptic peritonitis, suggesting that COX-2 can enhance lymphangiogenesis in the absence of cancer cells. Our findings suggest that COX-2 inhibitor may be useful for prophylaxis of lymph node metastasis by reducing macrophage-mediated tumor lymphangiogenesis. [Cancer Res 2007;67(21):10181–9]
Upregulation of lymphotoxin expression in liver progenitor (oval) cells in chronic hepatitis C
Authors: K N Lowes
Journal: Gut (2003)

<b>Background:</b> Bipotent liver progenitor (oval) cells with the ability to differentiate into hepatocytes and biliary epithelium have recently been identified in human subjects with hepatitis C. Animal studies suggest that members of the tumour necrosis factor family, including lymphotoxin β (LT-β), regulate oval cell proliferation in liver disease, but its role in human liver disease is unclear. <b>Aims:</b> This study seeks to establish a role for LT-β in hepatitis C related liver injury and to provide evidence that its increased expression is related to the presence of oval cells. <b>Methods:</b> Liver biopsy specimens were obtained from patients with chronic hepatitis C virus (HCV) infection (n=20). Control liver samples (n=5) were obtained from liver resection or transplant surgery. LT-β expression in liver biopsy specimens was studied using quantitative real time polymerase chain reaction and immunohistochemistry. <b>Results:</b> LT-β mRNA levels were similar in control and HCV liver in the absence of fibrosis. In subjects with portal fibrosis, LT-β mRNA levels were elevated 2.2-fold over control liver levels (p=0.04). In subjects with bridging fibrosis, LT-β mRNA levels increased 4.4-fold over control liver levels (p=0.02). LT-β mRNA levels in subjects with established cirrhosis were increased 3.3-fold compared with controls and 2.6-fold compared with mild liver damage (p=0.02). Immunohistochemical analysis established that LT-β was expressed by oval cells, inflammatory cells, and small portal hepatocytes. <b>Conclusions:</b> In chronic HCV infection, LT-β expression is observed in multiple hepatic cell types, including oval cells. LT-β expression is significantly increased when fibrosis or cirrhosis is present, suggesting a role for LT-β in the pathogenesis of chronic hepatitis C and a possible role in oval cell mediated liver regeneration.
The Metallo-β-Lactamase/β-CASP Domain of Artemis Constitutes the Catalytic Core for V(D)J Recombination
Authors: Catherine Poinsignon, Despina Moshous, Isabelle Callebaut, Régina de Chasseval, Isabelle Villey, Jean-Pierre de Villartay
Journal: The Journal of Experimental Medicine (2004)

The V(D)J recombination/DNA repair factor Artemis belongs to the metallo-β-lactamase (β-Lact) superfamily of enzymes. Three regions can be defined within the Artemis protein sequence: (a) the β-Lact homology domain, to which is appended (b) the β-CASP region, specific of members of the β-Lact superfamily acting on nucleic acids, and (c) the COOH-terminal domain. Using in vitro mutagenesis, here we show that the association of the β-Lact and the β-CASP regions suffices for in vivo V(D)J recombination of chromosome-integrated substrates. Single amino acid mutants point to critical catalytic residues for V(D)J recombination activity. The results presented here define the β-Lact/β-CASP domain of Artemis as the minimal core catalytic domain needed for V(D)J recombination and suggest that Artemis uses one or two Zn(II) ions to exert its catalytic activity, like bacterial class B β-Lact enzymes hydrolyzing β-lactam compounds.
International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels
Authors: W. A. Catterall, K. G. Chandy, D. E. Clapham, G. A. Gutman, F. Hofmann, A. J. Harmar, D. R. Abernethy, M. Spedding
Journal: Pharmacological Reviews (2003)

This issue of Pharmacological Reviews includes a new venture in the collaboration between the International Union of Pharmacology (IUPHAR) and the American Society for Pharmacology and Experimental Therapeutics (ASPET), in that a new classification of voltage-gated ion channels is outlined in this
The Na+/H+exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction11This manuscript is dedicated to the memory of Karl-Ludwig Neuhaus (1944–2000).
Authors: Uwe Zeymer, Harry Suryapranata, Jean Pierre Monassier, Grzegorz Opolski, John Davies, Gundars Rasmanis, Gerard Linssen, Ulrich Tebbe, Rolf Schröder, Rolf Tiemann, Thomas Machnig, Karl-Ludwig Neuhaus
Journal: Journal of the American College of Cardiology (2001)
Therapy of metastatic carcinoid tumor and the malignant carcinoid syndrome with recombinant leukocyte A interferon.
Authors: C G Moertel, J Rubin, L K Kvols
Journal: Journal of Clinical Oncology (1989)

Twenty-seven patients with metastatic carcinoid tumor, 24 of whom had the malignant carcinoid syndrome, were treated with recombinant leukocyte A interferon at a planned dose of 24 x 10(6) U/m2. Twenty percent of patients with measurable tumor experienced an objective regression and 39% of those with the carcinoid syndrome experienced a reduction of more than 50% in urine 5-hydroxyindoleacetic acid (5HIAA) excretion. Flushing was partially or completely relieved in 65% of patients and diarrhea was relieved in 33%. Regrettably, these favorable treatment effects were transient in nature, with objective regressions persisting for a median of only 7 weeks and hormonal responses for a median of only 4 weeks. Any therapeutic gain experienced by these patients seemed to be outweighed by the frequency and severity of toxic reactions, which consisted primarily of chills and fever, fatigue, anorexia, weight loss, leukopenia, and abnormalities of liver function. Whereas other interferons, administration by alternative dosages and regimens, or incorporation of interferons into drug combinations may merit future study, we cannot recommend recombinant leukocyte A interferon, administered by the methods we employed, for routine therapy of the carcinoid tumor or syndrome.
Cost-Effectiveness of Fluocinolone Acetonide Implant versus Systemic Therapy for Noninfectious Intermediate, Posterior, and Panuveitis
Authors: Elizabeth A. Sugar, Janet T. Holbrook, John H. Kempen, Alyce E. Burke, Lea T. Drye, Jennifer E. Thorne, Thomas A. Louis, Douglas A. Jabs, Michael M. Altaweel, Kevin D. Frick
Journal: Ophthalmology (2014)
Screening for pulmonary and cerebral arteriovenous malformations in children with hereditary haemorrhagic telangiectasia
Authors: S. Al-Saleh, M. Mei-Zahav, M. E. Faughnan, I. B. MacLusky, S. Carpenter, M. Letarte, F. Ratjen
Journal: European Respiratory Journal (2009)

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterised by vascular dysplasia complicated by visceral arteriovenous malformations (AVMs). To date, the diagnostic yield of screening procedures for pulmonary and cerebral AVMs in children with definite or potential HHT is not well defined. The aim of the present study was to prospectively evaluate the diagnostic yield of a screening protocol for pulmonary and cerebral AVMs in children with either a definite or potential HHT diagnosis. All children referred for evaluation for HHT between 1996 and 2008 were included in the present analysis. Screening tests for AVMs included chest computed tomography and brain magnetic resonance imaging. 61 children with a definite clinical and/or genetic diagnosis of HHT were asymptomatic for visceral AVMs at their first baseline assessment (mean± sd age 8.7±4.7 yrs; range 0–17.0 yrs). Of these, 15 (25%) had pulmonary and/or cerebral AVMs diagnosed on initial screening tests. Pulmonary AVMs predominated in paediatric HHT patients (14 out of 15 patients) and were found in eight children aged &lt;10 yrs. 55 children had a potential HHT diagnosis as they fulfilled only one or two HHT clinical diagnostic criteria and did not have a confirmatory genetic diagnosis (age 10.9±4.8 yrs; range 0–17.9 yrs). None of these children had pulmonary or cerebral AVMs on initial screening tests. The present data suggest that children with a definite HHT diagnosis have a high frequency of pulmonary AVMs even when clinically asymptomatic. In contrast, no AVMs were observed in children not fulfilling HHT diagnostic criteria. Genetic testing appears to be useful in defining an at-risk group for pulmonary AVMs in childhood.
Histocompatibility studies in a closely bred colony of dogs. V. Mechanisms of cellular adaptation in long-term DL-A identical radiation chimeras.
Authors: F T Rapaport, H S Lawrence, R Bachvaroff, F D Cannon, D Blumenstock, N Mollen, J H Ayvazian, J W Ferrebee
Journal: The Journal of Experimental Medicine (1975)

20 Cooperstown beagles of known DL-A genotypes (B" dogs) were exposed to supralethal total body irradiation and received a bone marrow allograft from a DL-A identical donor (A" dog); the resulting chimeras have survived uneventfully for 882, 1466 days, with no evidence of secondary disease, and have been tolerant to kidney and skin allografts obtained from the donor of marrow. Treatment of "A" dogs with serum obtained from their long-term "B" chimeras had no significant effect upon the ability of the recipients to reject "B" skin allografts...
PWE-046 Early Clinical Experience of Endoclot™ in the Treatment of Acute Gastro-Intestinal Bleeding
Authors: K Halkerston, J Evans, D Ismail, S Catnach, R Chaudhary, M Fullard, A King, A Leahy
Journal: Gut (2013)

<h3>Introduction</h3> EndoClot<b>™</b> is a new novel haemostatic powder for the treatment of gastrointestinal bleeding. We report our initial experiences of EndoClot<b>™</b> as an adjunct haemostatic therapy. This is the first UK report of its endoscopic use in gastrointestinal bleeding. <h3>Methods</h3> EndoClot™ was used as an adjunct therapy in the treatment of continued bleeding following a therapeutic intervention, either for acute upper gastrointestinal bleeds, or after elective endoscopic mucosal resections. Up to 1g of AMP® (absorbable modified polymers) was applied in each patient using the EndoClot™ air compressor and applicator. <h3>Results</h3> EndoClot™ was used in a total of 6 patients, (5 men, 1 woman; aged between 49 and 83 years, mean age 68 years). In 2 patients, EndoClot™ was applied following endoscopic mucosal resection of a rectal polyp after bleeding was not resolved with cautery. In a further 2 patients, EndoClot™ was applied over a duodenal ulcer with endoscopic stigmata of recent haemorrhage when there was residual bleeding despite adrenaline injection and gold probe cautery. In another patient, EndoClot™ was applied following clipping of a spurting vessel at the gastro-oesophageal junction (likely Mallory-Weiss tear). In these 5 patients, application of EndoClot™ resolved any continued bleeding. There was also no rebleeding within 14 days of the procedure, no mortality or major adverse events. A sixth patient had EndoClot™ applied to what was first thought to be a duodenal ulcer with a probable vessel, when there was residual bleeding despite adrenaline injection and gold probe cautery. This patient was re-scoped the following day after further bleeding and subsequent investigations confirmed a carcinoma of the pancreatic head with duodenal infiltration. <h3>Conclusion</h3> EndoClot™ appears to be a safe and effective adjunct to existing therapies in the treatment of gastrointestinal bleeding. Large prospective studies are required to establish its exact role alongside established methods of haemostasis. <h3>Disclosure of Interest</h3> None Declared.
Adult Community-Acquired Pneumonia in Central London
Authors: W R McNabb, D C Shanson, T D M Williams, A F Lant
Journal: Journal of the Royal Society of Medicine (1984)

Strep. pneumoniae was diagnosed as the cause of pneumonia in 40 (50%) of 80 consecutive adults admitted to St Stephen's Hospital with community-acquired pneumonia. None of the patients had evidence of Mycoplasma pneumoniae infection, and Legionella pneumophila serology was positive on only one occasion. In 29 patients (36%) no causative organism was demonstrated. The diagnosis of pneumococcal infection was obtained in 15 cases by isolating Strep. pneumoniae from the sputum, in 13 further cases by demonstrating pneumococcal capsular antigen in sputum, and in 12 other cases by detecting pneumococcal antigen in serum only. Only 2 cases with pneumococcal pneumonia were bacteraemic and 3 patients (7%), all aged more than 75 years, died. The relatively low bacteraemic and mortality rates suggest that community-acquired pneumococcal pneumonia currently seen in patients admitted to hospital in central London may not be so severe as in some other areas.
Strategies for viral RNA stability: live long and prosper
Authors: Alexa M. Dickson, Jeffrey Wilusz
Journal: Trends in Genetics (2011)

Eukaryotic cells have a powerful RNA decay machinery that plays an important and diverse role in regulating both the quantity and the quality of gene expression. Viral RNAs need to successfully navigate around this cellular machinery to initiate and maintain a highly productive infection. Recent work has shown that viruses have developed a variety of strategies to accomplish this, including inherent RNA shields, hijacking host RNA stability factors, incapacitating the host decay machinery and changing the entire landscape of RNA stability in cells using virally encoded nucleases. In addition to maintaining the stability of viral transcripts, these strategies can also contribute to the regulation and complexity of viral gene expression as well as to viral RNA evolution.
Human monocyte-derived mucus secretagogue.
Authors: Z Marom, J H Shelhamer, M Kaliner
Journal: Journal of Clinical Investigation (1985)

Human peripheral monocytes were stimulated with opsonized zymosan or protein A-containing Staphylococcus aureus to examine whether factors might be released that were capable of stimulating mucous glycoprotein release from cultured human airways, as has recently been described with human pulmonary macrophages. While the supernatant from monocytes exposed to opsonized zymosan or protein A-containing S. aureus caused an impressive activity was found in the control samples that were cultured in parallel and exposed to nonactivated zymosan or S. aureus that was deficient in protein A. The responsible factor was termed monocyte-derived mucus secretagogue (MMS). The maximum MMS release was reached 4-8 h after stimulation, and the amount of MMS released was dependent on the dose of opsonized zymosan added. Chromatographic analyses of MMS indicate that its molecular weight was approximately 2,000 and that the isoelectric point (pI) was 5.2, with a smaller second peak of 7.4 on isoelectric focusing. MMS itself was not detected in monocyte lysates, nor was it formed by monocytes treated with the protein synthesis inhibitor, cycloheximide, before exposure to activating particles. MMS was not a prostaglandin, could not be extracted into organic solvents, and is probably not an eicosanoid. Based on these observations, we conclude that stimulated human peripheral monocytes synthesize a small, acidic molecule, termed MMS, that is capable of stimulating human airways to secrete mucus and in nearly every respect is identical to pulmonary macrophage-derived MMS.
Decreased density of serotonin 5-HT2A receptors in rheumatoid arthritis
Authors: A Kling
Journal: Annals of the Rheumatic Diseases (2006)

Animal studies have indicated that 5-HT2A receptors could play a role in arthritic diseases.To analyse the binding properties of 5-HT2A receptors in patients with rheumatoid arthritis.Using a radioactive binding assay, 43 patients with rheumatoid arthritis were compared with 49 sex and age matched controls for density and affinity (measured as Bmax and Kd) of 5-HT2A serotonin receptors. Genotyping, using polymerase chain reaction, was undertaken to exclude the possibility that differences in the genetic polymorphism T102C for the 5-HT2A receptor determine differences in receptor density.Mean of Bmax of 5-HT2A receptors in rheumatoid patients was significantly lower than in controls, at 45.3 v 57.4 fmol/mg protein (p = 0.004), but there was no significant difference in Kd. The T102C receptor polymorphism genotypes showed a skewed distribution between the two groups. Even when adjusted for this, there was a significant difference in Bmax between the groups.The density of 5-HT2A serotonin receptors in patients with rheumatoid arthritis is markedly reduced. This could either reflect a difference involved in the susceptibility to the disease or be a secondary effect of the disease.