tbuckley/cabot-search huggingface dataset:
Histone Deacetylase 3 Is Critical in Endothelial Survival and Atherosclerosis Development in Response to Disturbed Flow
Authors: Anna Zampetaki, Lingfang Zeng, Andriana Margariti, Qingzhong Xiao, Hongling Li, Zhongyi Zhang, Anna Elena Pepe, Gang Wang, Ouassila Habi, Elena deFalco, Gillian Cockerill, Justin C. Mason, Yanhua Hu, Qingbo Xu
Journal: Circulation (2009)

Histone deacetylase 3 (HDAC3) is known to play a crucial role in the differentiation of endothelial progenitors. The role of HDAC3 in mature endothelial cells, however, is not well understood. Here, we investigated the function of HDAC3 in preserving endothelial integrity in areas of disturbed blood flow, ie, bifurcation areas prone to atherosclerosis development.En face staining of aortas from apolipoprotein E-knockout mice revealed increased expression of HDAC3, specifically in these branching areas in vivo, whereas rapid upregulation of HDAC3 protein was observed in endothelial cells exposed to disturbed flow in vitro. Interestingly, phosphorylation of HDAC3 at serine/threonine was observed in these cells, suggesting that disturbed flow leads to posttranscriptional modification and stabilization of the HDAC3 protein. Coimmunoprecipitation experiments showed that HDAC3 and Akt form a complex. Using a series of constructs harboring deletions, we found residues 136 to 206 of HDAC3 to be crucial in this interaction. Enforced expression of HDAC3 resulted in increased phosphorylation of Akt and upregulation of its kinase activity. In line with these findings, knockdown of HDAC3 with lentiviral vectors (shHDAC3) led to a dramatic decrease in cell survival accompanied by apoptosis in endothelial cells. In aortic isografts of apolipoprotein E-knockout mice treated with shHDAC3, a robust atherosclerotic lesion was formed. Surprisingly, 3 of the 8 mice that received shHDAC3-infected grafts died within 2 days after the operation. Miller staining of the isografts revealed disruption of the basement membrane and rupture of the vessel.Our findings demonstrated that HDAC3 serves as an essential prosurvival molecule with a critical role in maintaining the endothelial integrity via Akt activation and that severe atherosclerosis and vessel rupture in isografted vessels of apolipoprotein E-knockout mice occur when HDAC3 is knocked down.
Adverse reactions during treatment with amiodarone hydrochloride
Authors: P J M Sloan, S P Singh, P G Bevan, J. Gearty
Journal: BMJ (1983)

<h3>Abstract</h3> Type-II Toxin Antitoxin (TA) systems are regulated by differential half-lives of the resulting non-secreted proteins, such that the neutralizing antitoxin undergoes continual degradation and replenishment to maintain neutralization of its cognate toxin. Antitoxin proteins are widely reported as labile, including upon purification and <i>in vitro</i> storage. During the course of studies on a ParDE TA system we noted a prevalent <i>in vitro</i> degradation of the ParD antitoxin. In efforts to combat this for practical use in assays, we characterized parameters impacting the degradation as well as the resulting products. These revealed a mechanism likely mediated by a serine or metal-dependent protease. Using Direct Infusion Mass Spectrometry, the cleavage products were identified as an essentially intact DNA binding region of the antitoxin and with the toxin binding domain completely removed. No other species were identified in the solution, such as a contaminant that may mediate such cleavage. Therefore, while our studies revealed viable strategies to mitigate the <i>in vitro</i> degradation they did not identify any protease, leaving open the possibility of a potential auto-catalytic proteolytic activity of the antitoxin proteins.
Do GPs deserve their recent pay rise?
Authors: Nicholas Timmins
Journal: BMJ (2005)

<b>Background:</b> Cardiovascular disease (CVD) is a common co-morbidity in patients with chronic obstructive pulmonary disease (COPD), but the relationship between acute exacerbation requiring COPD hospitalisation (AECOPD) and subsequent risk of CV morbidity or mortality is unclear, particularly in low and middle income countries. <b>Objectives:</b> To examine the risk of CV events following first hospitalized AECOPD. <b>Methods:</b> A prospective cohort included &gt;0.5M men and women, aged 30-79 years who were recruited from ten diverse areas (5 rural and 5 urban) in China during 2004-8 and followed up for a mean of 7 years through linkage to death registries and hospital records. We analyzed data from 489,382 participants without prior history of CVD. Cox regression model was used to yield adjusted hazard ratios (HRs) relating hospital admission of incident AECOPD to subsequent incident CVD events. <b>Results:</b> Overall, 10,657 participants were admitted to hospital with a first AECOPD, among them the risk of subsequent CV events (n=1384) were subsequently increased, with adjusted HRs of 1.70 (95% CI 1.56-1.84), 1.69 (1.53-1.87), 1.44 (1.18-1.75), 2.68 (2.27-3.16), 6.85 (5.65-8.32) and 1.89 (1.66-2.15) for major vascular events, ischaemic stroke , haemorrhagic stroke , major coronary events, congestive heart failure and CVD death respectively. Of the CVD events recorded, over 85% of these occurred within 28 days of AECOPD: <b>Conclusion:</b> Among adult Chinese, AECOPD leading to hospitalisation was independently associated with an increased risk of subsequent incident CVD events, especially in the first 28 days post-COPD hospitalisation. (Funded by GSK).
Abstract LB-246: Dietary strawberry phytochemical metabolism in saliva, urine, and genetic biomarkers in smokers and non-smokers
Authors: Jennifer H. Ahn-Jarvis, Steven K. Clinton, Kenneth M. Riedl, Marta T. Sears, Thomas J. Knobloch, Steven J. Schwartz, Christopher M. Weghorst, Yael Vodovotz
Journal: Cancer Research (2014)

Abstract Background: Epidemiological studies implicate tobacco smoke and alcohol consumption are critical risk factors for oral cancer. Yet diets rich in strawberries have shown in rodent and cell studies to have significant protective effects which lower the risk of oral cancer. A fully-characterized strawberry confection was evaluated for safety and adherence in a 6-week, randomized, placebo-controlled, crossover trial involving smokers (n=12) and non-smokers (n=13). Methods: Using HPLC with tandem mass spectroscopy, strawberry phytochemicals in strawberry powder, confection and saliva collected during a 30 minute timed intervention were fully characterized. Buccal tissue was evaluated using pre-validated TaqMan Gene Expression assays corresponding to known smoke-altered oral transcriptome biomarkers used for RT-qPCR analysis. UPLC with mass spectroscopy quantified ellagic acid metabolites (dimethyl-, isourolithin A, urolithin A, B, and C) in 24hr urine collections. Results: Adherence strawberry confections intervention (equivalent to 2 cups of whole strawberries) in smoker (91%) and nonsmokers (99%) was excellent. Toxicities to strawberry intervention was limited to a grade I toxicity (NIH criteria). Significantly less ellagic acid and ellagitannins were observed in saliva compared to confection (p&amp;lt;0.001). Anthocyanin profiles in saliva of smokers differed significantly than non-smokers. One biomarker, Ankyrin Repeat Domain 37 (ANKRD37), was found to be significantly down-regulated in smokers following strawberry confection intervention (p=0.0484). Significant increase (p&amp;lt;0.001) in urolithin A (4.29 ± 1.16 nmol/24hr) and C (0.13 ± 0.03 nmol/24hr) was observed in all participants after strawberry intervention compared to anthocyanin-free diet or placebo intervention. Isourolithin A and urolithin B was observed in 29% and 24% of participants, respectively. Conclusions: A fully characterized strawberry confection was utilized and significant changes in biomarkers of strawberry exposure from saliva, urine and genomic materials were observed. Both ellagitannin metabolites, urolithin A and C would be reliable biomarkers of strawberry exposure. Moreover, differences in ellagitannin metabolite profiles and in ANKRD37 between smokers and non-smokers warrant further studies. Citation Format: Jennifer H. Ahn-Jarvis, Steven K. Clinton, Kenneth M. Riedl, Marta T. Sears, Thomas J. Knobloch, Steven J. Schwartz, Christopher M. Weghorst, Yael Vodovotz. Dietary strawberry phytochemical metabolism in saliva, urine, and genetic biomarkers in smokers and non-smokers. [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 LB-246. doi:10.1158/1538-7445.AM2014-LB-246
Thermotherapy of Prostate Cancer Using Magnetic Nanoparticles: Feasibility, Imaging, and Three-Dimensional Temperature Distribution
Authors: Manfred Johannsen, Uwe Gneveckow, Burghard Thiesen, Kasra Taymoorian, Chie Hee Cho, Norbert Waldöfner, Regina Scholz, Andreas Jordan, Stefan A. Loening, Peter Wust
Journal: European Urology (2006)
Recombinant activated factor VII (rFVIIa) therapy for intracranial hemorrhage in hemophilia a patients with inhibitors
Authors: M. L. Schmidt, S. Gamerman, H. E. Smith, J. P. Scott, D. M. DiMichele
Journal: American Journal of Hematology (1994)

We report the use of recombinant VIIa (rFVIIa) in the treatment of five ICHs in two factor VIII-deficient patients with inhibitors. In four of five ICHs, rFVIIa was the only factor replacement used at doses of 60-135 micrograms/kg every 2-4 hr for 12-14 days. Hemostasis at the primary site of bleeding was achieved in all cases, and all patients survived with no permanent neurologic deficits. However, the patient who received the highest dose of rFVIIa during the first 4 days of therapy developed clinical symptoms consistent with a cerebral vascular accident of the brainstem characterized by acute onset of truncal ataxia and upward-gaze nystagmus on day 8 of rFVIIa therapy. While receiving rFVIIa therapy for treatment of these five ICHs, four treatment courses were complicated by bleeding at sites other than the primary site, including two episodes of localized oozing at central line insertion sites, two episodes of hemarthrosis, and two episodes of epistaxis. Antifibrinolytic therapy with tranexamic acid was effective in two of these episodes. Laboratory evaluation revealed shortening of the PT, variable shortening without normalization of the APTT, peak factor VII activity levels 7-30-fold higher than normal baseline values, and normal antithrombin III (ATIII) and alpha 2-antiplasmin levels. In four of five ICHs, there was a 20-40% decrease in fibrinogen levels from baseline. The decrease in fibrinogen was accompanied by an increase in fibrin degradation products in 3/5 episodes and a 15-35% decrease in plasminogen activity levels in 2/5 episodes. Tissue factor pathway inhibitor (TFPI) levels remained stable and in the normal range. Although rFVIIa is an effective new therapy for the treatment of ICH in hemophilia patients with inhibitors, its optimal use with respect to safety and efficacy requires further clinical study.
Methadone-Induced Pulmonary Edema
Authors: Maxwell S. Maillis
Journal: JAMA (1972)

To the Editor.—  The article by Kjeldgaard et al (218:882, 1971) on Methadone-Induced Pulmonary Edema was of interest in view of our recent experience with a similar patient. That morphine and heroin may cause an identical picture is, as the authors state, well documented, but it should also be noted that methadone has previously been reported to produce pulmonary edema.  Gardner1in reviewing the postmortem findings, laboratory analyses, and hospital records of 12 patients who died from methadone overdosage found that pulmonary edema was present in all cases. Methadone was the only agent identified in five cases, whereas the coincidental misuse of another drug occurred in the remaining seven patients.
Doctors in Germany will have to charge patients 10 a visit
Authors: A. Tuffs
Journal: BMJ (2003)

Doctors in Germany are protesting at being asked to collect €;10 (£7; $12) from all patients attending their practices from January next year. The payments will then be passed on to the country's health insurance companies.

Doctors want to be paid for the additional administrative work and want to be protected from any financial risk involved if patients do not pay.

A final decision relating to the scheme will be taken …
Abstract 724: New fluorescence-based cell assays for visualizing the Raf - Ras interaction and the Wnt pathway activity.
Authors: Johanna N. Apfel, Patricia T. Reischmann
Journal: Cancer Research (2013)

Abstract Colorectal cancer (CRC) belongs to the most frequent cancer types (Hollande et al. 2010). As molecular mechanism for CRC, several mechanisms are presumed, including chromosome instability going along with the inactivation of the adenomatous polyposis coli (APC) gene, a key protein of Wnt signaling (Thorstensen et al. 2005). It is widely accepted that an abnormally activated Wnt pathway is a major cause for non-braked proliferation and for reduced cell differentiation. The second major cause of CRC is the deregulation of genes affecting the Ras pathway (Jeremy R. Jass, 2006). Nevertheless, specific drugs targeting either the Wnt or the Ras pathways are rare. Therefore, we designed new, fluorescence-based reporter gene assays either for the Wnt or the Ras/Raf pathway as tools to simplify the screening for compounds modifying each pathway. Such cellular systems could be applicable for high-throughput-screening as well as Live-Cell-Imaging of compound effects, as shown in preliminary experiments. Therein, stably transfected HEK 293T cells bearing the new, Wnt-responsive reporter gene vector, were treated with LiCl, Wnt3a protein or acetylsalicylic acid in order to get a specific response. Cells showed an increase of the fluorescence level, which is measurable by a standard ELISA reader and could be visualized via fluorescence microscopy. In MDCK or MDCK-F3 cells bearing the Raf-responsive element, treated with EGF or a Raf inhibitor, the localization of the fluorescence signal changed. Moreover, treating the cells with different combination of the mentioned Wnt- or Ras-active compounds also showed a response, indicating a correlation between the two pathways. These results lead to the conclusion to combine both reporter gene vectors in order to detect the interplay of the pathways. Besides sensibilization of the assays and setting up the Live-Cell imaging experiments, this will be our further steps. In summary, we designed several assays applicable in a screening assay for new, specific compounds targeting the two most important cancer-related pathways Wnt and Ras/Raf. Such an assay is more cost-effective than conventional assays, and also offers the possibility to characterize directly the biochemical mechanisms and interplays via Live-Cell-Imaging. Citation Format: Johanna N. Apfel, Patricia T. Reischmann. New fluorescence-based cell assays for visualizing the Raf - Ras interaction and the Wnt pathway activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 724. doi:10.1158/1538-7445.AM2013-724
Dose-Finding Phase I Clinical and Pharmacokinetic Study of Orally Administered Irinotecan in Patients with Advanced Solid Tumors
Authors: Isa E.L.M. Kuppens, Eric Dansin, Henk Boot, Celine Feger, Sylvia Assadourian, Maria-Edith Bonneterre, Jos H. Beijnen, Jan H.M. Schellens, Jacques Bonneterre
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The aim of this study was to determine the daily maximum tolerated dose (MTD) and the dose-limiting toxicity for the following administration schedules: oral irinotecan given over 14 days every 3 weeks (part I) and oral irinotecan administered concomitantly with capecitabine over 14 days every 3 weeks (part II). In total, 42 patients (17 male and 25 female) with solid tumors refractory to standard therapy entered the study. Experimental Design: Treatment in part I consisted of irinotecan administered orally as semisolid matrix capsules at doses of 25, 30, and 35 mg/m2 once daily to confirm the MTD of our earlier study. In part II treatment, dose levels for irinotecan combined with capecitabine were 20/1,600, 25/1,600, 30/1,600, and 30/2,000 mg/m2/d. Results: The median number of cycles administered per patient was 2.0 (range, 1-12) in part I and 2.0 (range, 1-13) in study part II. Gastrointestinal toxicities (grade 3 nausea, grades 3 and 4 vomiting, and grades 3 and 4 diarrhea) were dose limiting in both parts of the study. There were no grade 3 or 4 hematologic toxicities. The MTD was 30 mg/m2/d for irinotecan single agent and 30/1,600 mg/m2/d for the combination with capecitabine. Absorption of irinotecan was rapid, and peak concentrations of irinotecan and metabolite SN-38 were reached within 0 to 3 and 1.5 to 4.0 hours, respectively. Conclusions: In conclusion, oral irinotecan and capecitabine is feasible and well tolerated, and the recommended dose for phase II studies is 30/1,600 mg/m2/d administered daily for 14 days every 3 weeks.
Death of a hospital
Authors: Kelly KyungHwa Park
Journal: BMJ (2010)

We were a diverse group, from all over the country, pursuing different medical specialties—radiology, anaesthesia, dermatology, pain management and rehabilitation, ophthalmology, neurology—but united by the requirement of an intern year and the opportunity to enjoy, transiently, life in the big city, New York. What we didn’t know was that we would also have to mourn the death of our hospital.

I could easily wax poetic on the hospital’s brilliant 160 year history, complete with roles in the Titanic and 9/11 disasters, to being the home of the first cardiac critical care unit in the United States and a world renowned HIV clinic, to having “detoxed” Dylan Thomas, and giving Edna St Vincent Millay her …
A novel practical scoring for early diagnosis of traumatic bowel injury without obvious solid organ injury in hemodynamically stable patients
Authors: Ahmad Zarour, Ayman El-Menyar, Mazen Khattabi, Raed Tayyem, Osama Hamed, Ismail Mahmood, Husham Abdelrahman, William Chiu, Hassan Al-Thani
Journal: International Journal of Surgery (2014)
Campylobacter pylori in a sample of Finnish population: relations to morphology and functions of the gastric mucosa.
Authors: M Siurala, P Sipponen, M Kekki
Journal: Gut (1988)

The occurrence of Campylobacter pylori (CP) was examined in 179 subjects representing a sample collected from the population of South Finland. In a normal antral and body mucosa CP was present in 5% and 11% and in superficial gastritis (SG) in 71% and 91% of subjects, respectively. In atrophic gastritis (AG) of antrum and body the prevalence of CP decreased significantly with an increasing degree of atrophy, so that CP was not found in severe body AG. Different combinations of antral and body gastritis revealed a characteristic pattern. Campylobacter pylori was lacking when antral and body mucosa were normal, but was present in 41% when normal mucosa was associated with gastritis in the opposite area. In SG affecting diffusely antrum and body, the bacterium was present in every case, but when SG was associated with AG in the opposite area it was lacking in 29% of the subjects. When SG affecting both areas was compared with SG accompanied by different degrees of AG in the body, there was a highly significant decrease of the prevalence of CP in antrum and body along with an increasing degree of AG in the body. This decrease showed a highly significant positive correlation with the acid output. On the whole, acid output correlated well with the occurrence of CP in both antrum and body. Thus the prevalence of CP was 10% in achlorhydria and rose up to 100% in cases with acid output above 30 mmol/h. The presence of CP did not correlate with signs of acute inflammation, but correlated significantly with those of chronic inflammation. No correlation was found in the antrum and a significant negative one in the body, between CP infestation and the extension of intestinal metaplasia. It is concluded that increased pH of gastric contents and mucus secreted by intestinalised glands may create unfavourable conditions for survival of the bacteria and might explain the decrease in the prevalence of CP in the more severe degrees of AG. The present results, however, give no definite answer to the question of the pathogenic significance of CP in the development of chronic gastritis.
Discordant Uptake of Three Different Agents for Liver Scintigraphy in a Patient With Focal Nodular Hyperplasia
Authors: ALI S. ARBAB, KIYOSH KOIZUM, SACHIKO HIRAIKE, TAKAO ARAI, KEISUKE MERA, KUNI OHTOMO, TAKAO AINOTA, YOSHIHIRO AKAHANE, TOMOYOSH UETAKE
Journal: Clinical Nuclear Medicine (1995)

Focal nodular hyperplasia of the liver is composed of hepatocytes, variable amounts of Kupffer cells, and bile ducts. The amount of Kupffer cells per unit volume of tissue determines the uptake of Tc-99m phytate. However, the uptake of Tc-99m DTPA galactosyl human serum albumin (Tc-99m GSA) depends on the presence of normally functioning hepatocytes, and the uptake and excretion of Tc-99m pyridoxyledene-5-methyl tryptophan (Tc-99m PMT) depends on the presence of normally functioning hepatocytes as well as the patency of bile ducts. In this proven case of focal nodular hyperplasia, there was no uptake of Tc-99m phytate, but mildly decreased uptake of Tc-99m GSA and increased uptake of Tc-99m PMT were observed, compared to normal liver tissue. These are exceptional findings for focal nodular hyperplasia and mimicked those of a hepatic adenoma.
Cardiovascular Risks to Young Persons on the Athletic Field
Authors: Barry J. Maron
Journal: Annals of Internal Medicine (1998)

Sudden cardiac deaths of young athletes, which are usually associated with physical exertion, continue to achieve high public visibility and generate considerable concern.Despite broad community participation in sports, such catastrophes are uncommon, occurring in about 1/200 000 high school athletes per academic year. Various unsuspected congenital cardiovascular diseases are usually responsible; the most common lesions are hypertrophic cardiomyopathy and several congenital coronary artery anomalies. Selected reports suggest that arrhythmogenic right ventricular dysplasia may be a more common cause of these deaths than previously suspected. In some trained athletes with borderline increases in thickness of the left ventricular wall, mild morphologic expression of hypertrophic cardiomyopathy can often be distinguished from the physiologic consequences of athlete's heart by noninvasive clinical assessment and testing. In addition, the recognized cardiovascular risks of the athletic field are now extended to include cardiac arrest resulting from relatively modest, nonpenetrating chest blows produced by projectiles (such as baseballs) or bodily contact in the absence of underlying cardiac disease and without structural injury to the chest wall or heart. These uncommon but usually fatal events seem to result when chest impact occurs precisely during the vulnerable phase of repolarization, and they may be reduced by use of softer baseballs. Preparticipation screening for cardiovascular disease, consisting of standard history and physical examination, is customary practice for most high school and college athletes in the United States.Evidence suggests, however, that the present screening process for cardiovascular disease in high school athletes may be largely inadequate, given the content of the approved screening questionnaires (which serve as guidelines for the process) and the use of examiners with little cardiovascular training. This emphasizes the need for national standardization of preparticipation screening. The recommendations of the 26th Bethesda Conference for disqualification from competitive athletics are now a standard for management decisions when cardiovascular abnormalities are identified in trained athletes.