tbuckley/cabot-search huggingface dataset:
213Bi-[DOTA0, Tyr3]Octreotide Peptide Receptor Radionuclide Therapy of Pancreatic Tumors in a Preclinical Animal Model
Authors: Jeffrey P. Norenberg, Boudewijn J. Krenning, Inge R.H.M. Konings, Donna F. Kusewitt, Tapan K. Nayak, Tamara L. Anderson, Marion de Jong, Kayhan Garmestani, Martin W. Brechbiel, Larry K. Kvols
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The somatostatin analogue [DOTA0, Tyr3]octreotide (DOTATOC) has previously been labeled with low linear energy transfer (LET) β-emitters, such as 177Lu or 90Y, for tumor therapy. In this study, DOTATOC labeled with the high-LET α-emitter, 213Bi, was evaluated. Experimental Design: The radiolabeling, stability, biodistribution, toxicity, safety, and therapeutic efficacy of 213Bi-DOTATOC (specific activity 7.4 MBq/μg) were investigated. Biodistribution studies to determine somatostatin receptor specificity were done in Lewis rats at 1 and 3 hours postinjection. Histopathology of various organs was used to evaluated toxicity and safety. Therapeutic efficacy of 4 to 22 MBq 213Bi-DOTATOC was determined in a rat pancreatic carcinoma model. Results: Radiolabeling of the 213Bi-DOTATOC was achieved with radiochemical purity &amp;gt;95% and an incorporation yield ≥99.9%. Biodistribution data showed specific binding to somatostatin receptor–expressing tissues. Administration of free 213Bi, compared with 213Bi-DOTATOC, resulted in higher radioactivity accumulation at 3 hours postinjection in the kidneys [34.47 ± 1.40% injected dose/g (ID/g) tissue versus 11.15 ± 0.46%, P &amp;lt; 0.0001] and bone marrow (0.31 ± 0.01% ID/g versus 0.06 ± 0.02%, P &amp;lt; 0.0324). A significant decrease in tumor growth rate was observed in rats treated with &amp;gt;11 MBq of 213Bi-DOTATOC 10 days postinjection compared with controls (P &amp;lt; 0.025). Treatment with &amp;gt;20 MBq of 213Bi-DOTATOC showed significantly greater tumor reduction when compared with animals receiving &amp;lt;11 MBq (P &amp;lt; 0.02). Conclusions: 213Bi-DOTATOC showed dose-related antitumor effects with minimal treatment-related organ toxicity. No acute or chronic hematologic toxicities were observed. Mild, acute nephrotoxicity was observed without evidence of chronic toxicity. 213Bi-DOTATOC is a promising therapeutic radiopharmaceutical for further evaluation.
Myocardial <i>Smad4</i> Is Essential for Cardiogenesis in Mouse Embryos
Authors: Lanying Song, Wensheng Yan, Xinbin Chen, Chu-xia Deng, Qin Wang, Kai Jiao
Journal: Circulation Research (2007)

Congenital heart diseases are the most commonly observed human birth defects and are the leading cause of infant morbidity and mortality. Accumulating evidence indicates that transforming growth factor-beta/bone morphogenetic protein signaling pathways play critical roles during cardiogenesis. Smad4 encodes the only common Smad protein in mammals, which is a critical nuclear mediator of transforming growth factor-beta/bone morphogenetic protein signaling. The aim of this work was to investigate the roles of Smad4 during heart development. To overcome the early embryonic lethality of Smad4(-/-) mice, we specifically disrupted Smad4 in the myocardium using a Cre/loxP system. We show that myocardial-specific inactivation of Smad4 caused heart failure and embryonic lethality at midgestation. Histological analysis revealed that mutant mice displayed a hypocellular myocardial wall defect, which is likely the primary cause for heart failure. Both decreased cell proliferation and increased apoptosis contributed to the myocardial wall defect in mutant mice. Data presented in this article contradict a previous report showing that Smad4 is dispensable for heart development. Our further molecular characterization showed that expression of Nmyc and its downstream targets, including cyclin D1, cyclin D2, and Id2, were downregulated in mutant embryos. Reporter analysis indicated that the transcriptional activity of the 351-bp Nmyc promoter can be positively regulated by bone morphogenetic protein stimulation and negatively regulated by transforming growth factor-beta stimulation. Chromatin immunoprecipitation analysis revealed that the Nmyc promoter can form a complex with Smad4, suggesting that Nmyc is a direct downstream target of Smad4. In conclusion, this study provides the first mouse model showing that Smad4 plays essential roles during cardiogenesis.
Robotic Partial Nephrectomy with Superselective Versus Main Artery Clamping: A Retrospective Comparison
Authors: Mihir M Desai, Andre Luis de Castro Abreu, Scott Leslie, Jei Cai, Eric Yi-Hsiu Huang, Pierre-Marie Lewandowski, Dennis Lee, Arjuna Dharmaraja, Andre K Berger, Alvin Goh, Osamu Ukimura, Monish Aron, Inderbir S Gill
Journal: European Urology (2014)
Real-Time 2-Photon Imaging of Mitochondrial Function in Perfused Rat Hearts Subjected to Ischemia/Reperfusion
Authors: Madoka Matsumoto-Ida, Masaharu Akao, Toshihiro Takeda, Masashi Kato, Toru Kita
Journal: Circulation (2006)

Background— Mitochondria play pivotal roles in cell death; the loss of mitochondrial membrane potential (ΔΨ m ) is the earliest event that commits the cell to death. Here, we report novel real-time imaging of ΔΨ m in individual cardiomyocytes within perfused rat hearts using 2-photon laser-scanning microscopy, which has unique advantages over conventional confocal microscopy: greater tissue penetration and lower tissue toxicity. Methods and Results— The Langendorff-perfused rat heart was loaded with a fluorescent indicator of ΔΨ m , tetramethylrhodamine ethyl ester. Tetramethylrhodamine ethyl ester was excited with an 810-nm line of a Ti:sapphire laser, and its fluorescence in the heart cells was successfully visualized up to ≈50 μm from the epicardial surface. Taking advantage of this system, we monitored the spatiotemporal changes of ΔΨ m in response to ischemia/reperfusion at the subcellular level. No-flow ischemia caused progressive ΔΨ m loss and a more prominent ΔΨ m loss on reperfusion. During ischemia/reperfusion, cells maintained a constant ΔΨ m for the cell-to-cell specific period of latency, followed by a rapid, complete, and irreversible ΔΨ m loss, and this process did not affect the neighboring cells. Within a cell, ΔΨ m loss was initiated in a particular area of mitochondria and rapidly propagated along the longitudinal axis. These spatiotemporal changes in ΔΨ m resulted in marked cellular and subcellular heterogeneity of mitochondrial function. Ischemic preconditioning reduced the number of cells undergoing ΔΨ m loss, whereas cyclosporin A partially inhibited ΔΨ m loss in each cell. Conclusions— Investigation of cellular responses in the natural environment will increase knowledge of ischemia/reperfusion injury and provide deeper insights into antiischemia/reperfusion therapy that targets mitochondria.
Relationship between serum resistin concentrations and inflammatory markers in patients with type 2 diabetes mellitus
Authors: Huang Hui-bing, Kiyoshi Migita, Taichiro Miyashita, Yumi Maeda, Minoru Nakamura, Hiroshi Yatsuhashi, Hiromi Ishibashi, Katsumi Eguchi, Hironori Kimura
Journal: Metabolism (2006)
RE: Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk
Authors: Nelly Wion-Barbot, Didier Wion
Journal: JNCI Journal of the National Cancer Institute (2015)

Obesity is a risk factor for breast cancer in postmenopausal women. In their recent article, Gunter et al. found that associations between breast cancer risk and circulating levels of adipokines were null to modest. Importantly, they underscored that adipokines primarily function in a paracrine manner. Hence, adipokine plasma levels might be a poor surrogate for breast tissue levels (1). This is reminiscent of the situation observed with vitamin D. Obesity is inversely associated with vitamin D levels (2), and vitamin D inadequacy is observed in postmenopausal women (2). Moreover, 1,25-dihydroxyvitamin D (1,25D), the active metabolite of vitamin D, limits adipose tissue inflammation and suppresses leptin stimulation of cancer growth (3). As for adipokines, studies that have investigated the association between circulating levels of vitamin D and breast cancer risk gave mixed results (4,5). Could vitamin D and adipokines be two faces of the same coin? Vitamin D is barely active and requires two successive hydroxylations to produce 1,25D. The first hydroxylation is catalyzed in the liver by CYP2R1, the second one in the kidney by CYP27B1. This is the vitamin D endocrine system in which 1,25D is released in blood circulation and controls calcium homeostasis and skeletal health. Circulating 25(OH)-vitamin D levels between 50 and 75 nmol/L are considered indicative of vitamin D sufficiency. A paradigm shift recently occurred with the discovery of autocrine/paracrine vitamin D signaling in many tissues. In autocrine/paracrine systems, molecules are produced, act, and are degraded locally. Therefore, the autocrine/paracrine vitamin D signaling does not affect circulating levels of vitamin D metabolites. Two important features of the autocrine/paracrine vitamin D system are: 1) the regulation of CYP2R1 and CYP27B1 expression by inflammatory stimuli (6) and 2) the local storage of vitamin D in fat tissue (6). Hence, hydroxylated metabolites of vitamin D can be produced locally in response to inflammatory stimuli if sufficient local storage of vitamin D exists. Note that vitamin D
Complement metabolism in man: hypercatabolism of the fourth (C4) and third (C3) components in patients with renal allograft rejection and hereditary angioedema (HAE)
Authors: Charles B. Carpenter, Shaun Ruddy, Isam H. Shehadeh, Hans J. Müller-Eberhard, John P. Merrill, K. Frank Austen
Journal: Journal of Clinical Investigation (1969)

Highly purified and radioiodinated human C4 and (or) C3 were administered to patients with renal allografts in rejection, with hereditary angioedema (HAE), with chronic glomerulonephritis, and to control subjects. The latter group included normal individuals, anephric patients before transplantation, and stable renal allograft recipients. The catabolic rates of these complement proteins were determined by analysis of the disappearance of plasma protein-bound radioactivity (k(m)), and by direct measurement of urinary excretion of radioactivity (k(u)). The correlation coefficient between these two methods was 0.96. The mean +/-2 SD for catabolic rates in the control subjects was 0.9-2.7% plasma pool/hr for C4 and 0.9-2.0% plasma pool/hr for C3. Patients experiencing renal allograft rejection had unstable levels of C4 and C3, and exhibited moderate hypercatabolism of both proteins. One patient with chronic glomerulonephritis had hypercatabolism of C4 and C3 in the presence of stable normal serum levels. In patients with HAE who had extremely low levels of C4, catabolic rates for C4 were markedly elevated (3.7, 5.8, 7.0 and 8.8%/hr). Analysis of plasma curves in HAE revealed a three component disappearance curve instead of the two component curve in control subjects receiving the same preparation. Even though C3 levels were normal, moderate hypercatabolism of C3 was also present in HAE (2.6, 2.8, 2.8, and 3.2% of pool/hr). The marked hypercatabolism of C4 in HAE constitutes the first direct evidence for the in vivo destruction by uninhibited C1 esterase of its natural substrate C4. The moderate hypercatabolism of C3 is consistent with the in vivo formation of C3-convertase.
Reversal of antithrombotic agents
Authors: Kenneth A. Bauer
Journal: American Journal of Hematology (2012)

Abstract Anticoagulants are the mainstay of therapy for thromboembolic diseases. In addition to the more traditional agents, new oral anticoagulants, including dabigatran etexilate, rivaroxaban, and apixaban, have been shown to be effective across several indications. Bleeding is a serious complication associated with any anticoagulant, but many of the traditional parenteral and new oral agents do not currently have specific antidotes. This review describes available and future options for the reversal of the effects of anticoagulants, in particular the new oral agents and discusses current management strategies for bleeding events in clinical practice. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Role of histone deacetylases in vascular cell homeostasis and arteriosclerosis
Authors: B. Zhou, A. Margariti, L. Zeng, Q. Xu
Journal: Cardiovascular Research (2011)

Histone deacetylases (HDACs) are a family of enzymes that remove acetyl groups from lysine residues of histone proteins, a modification that results in epigenetic modulation of gene expression. Although originally shown to be involved in cancer and neurological disease, HDACs are also found to play crucial roles in arteriosclerosis. This review summarizes the effects of HDACs and HDAC inhibitors on proliferation, migration, and apoptosis of endothelial and smooth muscle cells. In addition, an updated discussion of HDACs' recently discovered effects on stem cell differentiation and atherosclerosis is provided. Overall, HDACs appear to be promising therapeutic targets for the treatment of arteriosclerosis and other cardiovascular diseases.
Loss of Consciousness at Onset of Subarachnoid Hemorrhage as an Important Marker of Early Brain Injury
Authors: Sureerat Suwatcharangkoon, Emma Meyers, Cristina Falo, J. Michael Schmidt, Sachin Agarwal, Jan Claassen, Stephan A. Mayer
Journal: JAMA Neurology (2015)

Loss of consciousness (LOC) is a common presenting symptom of subarachnoid hemorrhage (SAH) that is presumed to result from transient intracranial circulatory arrest.To clarify the association between LOC at onset of SAH, complications while in the hospital, and long-term outcome after SAH.A retrospective analysis was conducted of 1460 consecutively treated patients with spontaneous SAH who were part of a prospective observational cohort study at a large urban academic medical center (the Columbia University SAH Outcomes Project or SHOP). Patients were enrolled between August 6, 1996, and July 23, 2012. Analysis was conducted from December 1, 2013, to February 28, 2015.Loss of consciousness at onset was identified by structured interview of the patient and first responders. Patients (80.5%) were observed for up to 1 year to assess functional recovery.Modified Rankin scale scores were assigned based on telephone or in-person interviews of the patient, family members, or caregivers. Complications while in the hospital were predefined and adjudicated by the study team.Five hundred ninety patients (40.4%) reported LOC at onset of SAH. Loss of consciousness was associated with poor clinical grade, more subarachnoid and intraventricular blood seen on admission computed tomographic scan, and a higher frequency of global cerebral edema (P < .001). Loss of consciousness was also associated with more prehospital tonic-clonic activity (22.7% vs 4.2%; P < .001) and cardiopulmonary arrest (9.7% vs 0.5%, P < .001) vs patients who did not experience LOC. In multivariable analysis, death or severe disability at 12 months was independently associated with LOC after adjusting for established risk factors for poor outcome, including poor admission clinical grade (adjusted odds ratio, 1.94; 95% CI, 1.38-2.72; P < .001). There was no association between LOC at onset and delayed cerebral ischemia or aneurysm rebleeding.Loss of consciousness at symptom onset is an important manifestation of early brain injury after SAH and a predictor of death or poor functional outcome at 12 months.
Anomalous coronary origin: the challenge in preventing exercise-related sudden cardiac death
Authors: C P Edwards, A Yavari, M N Sheppard, S Sharma
Journal: British Journal of Sports Medicine (2010)

The sudden cardiac death (SCD) of a young athlete is a catastrophic event, particularly in the absence of prodromal warning symptoms. Anomalous coronary origin (ACO) is a well-described cause of cardiac symptoms and SCD, but the diagnosis is usually missed by conventional non-invasive investigations designed to identify myocardial ischaemia. SCD is preventable by correction of the anomaly. A tragic case of a promising young athlete who had underlying ACO and who presented with prodromal symptoms with multiple “negative” investigations is described to highlight the typical clinical features and outline the difficulties encountered in accurate premortem diagnosis.
Experimental bilateral lobar lung transplantation and its application in humans
Authors: J. P. Couetil, M. J. Tolan, A. Grousset, D. Benaim, M. Sapoval, A. Hernigou, P. Coppens, P. Fayolle, A. Carpentier
Journal: Thorax (1997)

The critical lack of donor organs from people of small size or children has created great difficulties in transplantation for recipients who are of smaller size. Surgical techniques of organ reduction and partial transplantation may to some extent solve the problem of disparity in organ size, be it liver or lung, and lessen the problem of scarcity of paediatric organs.In a series of experiments on dogs the surgical technique of pulmonary partition of a large organ from a grown dog followed by transplantation of lobes, either unilaterally or bilaterally, into a young dog was studied. Two series of experiments were performed in two groups of animals; in group 1 transplantation of a single right lobe (n = 6) or single left lobe (n = 6) from a split adult lung was carried out and in group 2 (n = 10) animals received bilateral lobar transplants from a single split adult lung. The animals were sacrificed at fixed intervals (days 8-120 in group 1, days 7-10 in group 2) and the results of the surgical technique were assessed.Healing of lobar bronchial anastomoses was found to be excellent with no histological evidence of dehiscence or ulceration. There was one bronchial anastomotic stenosis and one arterial thrombosis. Morphological and functional adaptation of the lobes in the thorax was found to be excellent in both groups of animals. The technique has been applied in a clinical setting and the first patient with bilateral lobar lung transplantation followed for 30 months is reported.Lung partition and subsequent lobar transplantation, either unilaterally or bilaterally, is associated with satisfactory early results in an animal experimental model. Initial clinical experience in one patient has been successful.
Ro-Associated Y RNAs in Metazoans: Evolution and Diversification
Authors: Jonathan Perreault, Jean-Pierre Perreault, Gilles Boire
Journal: Molecular Biology and Evolution (2007)

The Y genes encode small noncoding RNAs whose functions remain elusive, whose numbers vary between species, and whose major property is to be bound by the Ro60 protein (or its ortholog in other species). To better understand the evolution of the Y gene family, we performed a homology search in 27 different genomes along with a structural search using Y RNA specific motifs. These searches confirmed that Y RNAs are well conserved in the animal kingdom and resulted in the detection of several new Y RNA genes, including the first Y RNAs in insects and a second Y RNA detected in Caenorhabditis elegans. Unexpectedly, Y5 genes were retrieved almost as frequently as Y1 and Y3 genes, and, consequently are not the result of a relatively recent apparition as is generally believed. Investigation of the organization of the Y genes demonstrated that the synteny was conserved among species. Interestingly, it revealed the presence of six putative "fossil" Y genes, all of which were Y4 and Y5 related. Sequence analysis led to inference of the ancestral sequences for all Y RNAs. In addition, the evolution of existing Y RNAs was deduced for many families, orders and classes. Moreover, a consensus sequence and secondary structure for each Y species was determined. Further evolutionary insight was obtained from the analysis of several thousand Y retropseudogenes among various species. Taken together, these results confirm the rich and diversified evolution history of Y RNAs.
Injury prevention strategies at the FIFA 2014 World Cup: perceptions and practices of the physicians from the 32 participating national teams
Authors: Alan McCall, Michael Davison, Thor Einar Andersen, Ian Beasley, Mario Bizzini, Gregory Dupont, Rob Duffield, Chris Carling, Jiri Dvorak
Journal: British Journal of Sports Medicine (2015)

The available scientific research regarding injury prevention practices in international football is sparse. The purpose of this study was to quantify current practice with regard to (1) injury prevention of top-level footballers competing in an international tournament, and (2) determine the main challenges and issues faced by practitioners in these national teams.A survey was administered to physicians of the 32 competing national teams at the FIFA 2014 World Cup. The survey included 4 sections regarding perceptions and practices concerning non-contact injuries: (1) risk factors, (2) screening tests and monitoring tools, (3) preventative strategies and (4) reflection on their experience at the World Cup.Following responses from all teams (100%), the present study revealed the most important intrinsic (previous injury, accumulated fatigue, agonist:antagonist muscle imbalance) and extrinsic (reduced recovery time, training load prior to and during World Cup, congested fixtures) risk factors during the FIFA 2014 World Cup. The 5 most commonly used tests for risk factors were: flexibility, fitness, joint mobility, balance and strength; monitoring tools commonly used were: medical screen, minutes/matches played, subjective and objective wellness, heart rate and biochemical markers. The 5 most important preventative exercises were: flexibility, core, combined contractions, balance and eccentric.The present study showed that many of the National football (soccer) teams' injury prevention perceptions and practices follow a coherent approach. There remains, however, a lack of consistent research findings to support some of these perceptions and practices.
Chest radiology in cystic fibrosis: is scoring useful?
Authors: D J Shale
Journal: Thorax (1994)

Chest radiology in cystic fibrosis: is scoring useful?With the increasing survival in patients with cystic fibrosis and the primary cause of death in older patients being due to respiratory disease, there is renewed interest in the formalised scoring of chest radiographs.'Scoring systems have developed as part of an overall clinical assessment" and as specific staging scores for respiratory disease.5"8