tbuckley/cabot-search huggingface dataset:
Effects of branched-chain amino acid infusion on protein metabolism in rats with acute hepatic failure
Authors: Yoshiyuki Miwa, Masahiko Kato, Hisataka Moriwaki, Masataka Okuno, Jun'ichi Sugihara, Horoo Ohnishi, Takashi Yoshida, Yasutoshi Muto, Mitsuo Nakayama, Yujiro Morioka, Kouzou Asagi
Journal: Hepatology (1995)

Branched-chain amino acids (BCAA) are known to improve hepatic encephalopathy as well as protein malnutrition in cirrhosis. However, such effects in acute hepatic failure (AHF) remain to be elucidated. The current study was conducted to investigate whether BCAA improves protein metabolism in AHF. AHF was induced in male Donryu rats weighing approximately 230 g by giving 60 mg/kg lipopolysaccaride intravenously and 800 mg/kg D-galactosamine hydrochloride intraperitoneally. From 18 hours after injection, AHF rats and control rats were given one of the following five solutions intravenously for 6 hours: 1) saline, 2) 10% glucose, 3) standard 10% amino acid formula with total nitrogen content of 12.2 g/L and BCAA/aromatic amino acid molar ratio of 37.05, 4) BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 148.2, or 5) an active placebo against BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 37.05. In parallel, each group was given a continuous infusion of 14C-leucine. After the plasma radioactivity of 14C-leucine and the expired 14CO2 level reached a plateau, protein turnover was analyzed according to the kinetic model proposed previously by Waterlow. When compared with the control, rates of total protein turnover (total flux), oxidation, and breakdown all increased significantly in AHF. Infusion of standard 10% amino acid formula, BCAA-enriched solution or the placebo in AHF increased total flux and oxidation significantly as compared with the effect of saline or 10% glucose. Although saline, 10% glucose, standard 10% amino acid formula, and the placebo had no effect on synthesis rate, it was increased significantly with BCAA-enriched solution.(ABSTRACT TRUNCATED AT 250 WORDS)
Endogenous Markers of Two Separate Hypoxia Response Pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) Are Associated With Radiotherapy Failure in Head and Neck Cancer Patients Recruited in the CHART Randomized Trial
Authors: Michael I. Koukourakis, Søren M. Bentzen, Alexandra Giatromanolaki, George D. Wilson, Frances M. Daley, Michele I. Saunders, Stanley Dische, Efthimios Sivridis, Adrian L. Harris
Journal: Journal of Clinical Oncology (2006)

Randomized controlled trials have generally shown a benefit from accelerated radiotherapy in head and neck squamous cell carcinoma (HNSCC). However, the large randomized United Kingdom trial CHART (Continuous Hyperfractionated Accelerated Radiotherapy) failed to show a benefit of strongly accelerated over standard radiotherapy (RT) in 918 patients with HNSCC. In this study, we investigated the impact of tumor hypoxia on the outcome of HNSCC patients in the CHART trial. There are two distinct hypoxia inducible factors (HIFs) that control different gene response pathways and we assessed them both with endogenous markers of hypoxia, hypoxia inducible factor HIF-2 alpha (HIF-2) and carbonic anhydrase CA9, an indicator of HIF-1 alpha (HIF-1) function.Tissue from pre-RT biopsies performed in 198 of 918 patients recruited was analyzed for the immunohistochemical expression of HIF-2 and CA9.A significant association of high HIF2 and of high CA9 reactivity with poor locoregional control (P < .0001 and P = .0002, respectively) and poor survival (P = .0004 and 0.002, respectively) was noted. In multivariate analysis, HIF-2 and CA9 maintained their independent prognostic significance. Coexpression of both pathways had an additive effect, supporting their independent role. The uni-directional hypothesis, that a benefit from randomization to CHART should be seen in the nonhypoxic tumors, was supported by the data (one-tailed P = .04).Expression of endogenous markers of hypoxia for the HIF-1 and HIF-2 pathway is strongly associated with radiotherapy failure. Using immunohistochemical methods it is possible to identify subgroups of HNSCC patients who are highly curable with radiotherapy, or who are excellent candidates for clinical trials on hypoxia-targeting drugs in two distinct pathways.
Vitamin C Inhibits Endothelial Cell Apoptosis in Congestive Heart Failure
Authors: Lothar Rössig, Jörg Hoffmann, Bénédicte Hugel, Ziad Mallat, Astrid Haase, Jean-Marie Freyssinet, Alain Tedgui, Alexandra Aicher, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation (2001)

Background Proinflammatory cytokines like tumor necrosis factor-α and oxidative stress induce apoptotic cell death in endothelial cells (ECs). Systemic inflammation and increased oxidative stress in congestive heart failure (CHF) coincide with enhanced EC apoptosis and the development of endothelial dysfunction. Therefore, we investigated the effects of antioxidative vitamin C therapy on EC apoptosis in CHF patients. Methods and Results Vitamin C dose dependently suppressed the induction of EC apoptosis by tumor necrosis factor-α and angiotensin II in vitro as assessed by DNA fragmentation, DAPI nuclear staining, and MTT viability assay. The antiapoptotic effect of vitamin C was associated with reduced cytochrome C release from mitochondria and the inhibition of caspase-9 activity. To assess EC protection by vitamin C in CHF patients, we prospectively randomized CHF patients in a double-blind trial to vitamin C treatment versus placebo. Vitamin C administration to CHF patients markedly reduced plasma levels of circulating apoptotic microparticles to 32±8% of baseline levels, whereas placebo had no effect (87±14%, P &lt;0.005). In addition, vitamin C administration suppressed the proapoptotic activity on EC of the serum of CHF patients ( P &lt;0.001). Conclusions Administration of vitamin C to CHF patients suppresses EC apoptosis in vivo, which might contribute to the established functional benefit of vitamin C supplementation on endothelial function.
Mechanical Circulatory Support for Advanced Heart Failure
Authors: Mario C. Deng, Matthias Loebe, Aly El-Banayosy, Edoardo Gronda, Piet G. M. Jansen, Mario Vigano, Georg M. Wieselthaler, Bruno Reichart, Ettore Vitali, Alain Pavie, Thierry Mesana, Daniel Y. Loisance, Dereck R. Wheeldon, Peer M. Portner
Journal: Circulation (2001)

Use of wearable left ventricular assist systems (LVAS) in the treatment of advanced heart failure has steadily increased since 1993, when these devices became generally available in Europe. The aim of this study was to identify in an unselected cohort of LVAS recipients those aspects of patient selection that have an impact on postimplant survival.Data were obtained from the Novacor European Registry. Between 1993 and 1999, 464 patients were implanted with the Novacor LVAS. The majority had idiopathic (60%) or ischemic (27%) cardiomyopathy; the median age at implant was 49 (16 to 75) years. The median support time was 100 days (4.1 years maximum). Forty-nine percent of the recipients were discharged from the hospital on LVAS; they spent 75% of their time out of the hospital. For a subset of 366 recipients, for whom a complete set of data was available, multivariate analysis revealed that the following preimplant conditions were independent risk factors for survival after LVAS implantation: respiratory failure associated with septicemia (odds ratio 11.2), right heart failure (odds ratio 3.2), age >65 years (odds ratio 3.01), acute postcardiotomy (odds ratio 1.8), and acute infarction (odds ratio 1.7). For patients without any of these factors, the 1-year survival after LVAS implantation including the posttransplantation period was 60%; for the combined group with at least 1 risk factor, it was 24%.Careful selection, specifically implantation before patients become moribund, and improvement of management may result in improved outcomes of LVAS treatment for advanced heart failure.
Comparison of Afferent Activity of Canine Aortic and Sinus Nerves
Authors: Conrad L. Pelletier, Denis L. Clement, John T. Shepherd
Journal: Circulation Research (1972)

Pressure-dependent changes in afferent activity in the aortic and the sinus nerves were studied in 17 anesthetized dogs that were artificially ventilated with oxygen. Systemic arterial blood pressure was varied either continuously or in steps over the range of mean aortic blood pressure from 220 to 50 mm Hg with a pressurized reservoir connected to the abdominal aorta. Multifiber preparations from 20 aortic and 8 sinus nerves were used, and stimulusresponse curves were defined by measuring the mean impulse frequency at the various levels of pressure. Heart rate and pulse pressure were similar during recordings from both nerves. The two curves were S-shaped, with that for the aortic nerve being to the right of that for the sinus nerve. The change in activity was approximately linear from 200 to 120 mm Hg (mean aortic blood pressure) in the aortic nerve and from 180 to 80 mm Hg in the sinus nerve; there was no significant change in impulse frequency below mean blood pressures of 100 and 70 mm Hg, respectively. The threshold systolic blood pressure was 95 ± 3 (SE) mm Hg for the aortic receptors and 62 ± 4 mm Hg for the carotid sinus receptors. Thus, in the dog, the aortic baroreceptors are involved mainly in the control of high blood pressure, whereas at lower pressures the major control occurs through the carotid sinus baroreflex.
Oncoprotein EWS-FLI1 Activity Is Enhanced by RNA Helicase A
Authors: Jeffrey A. Toretsky, Verda Erkizan, Amy Levenson, Ogan D. Abaan, Jeffrey D. Parvin, Timothy P. Cripe, Anna M. Rice, Sean Bong Lee, Aykut Üren
Journal: Cancer Research (2006)

Abstract RNA helicase A (RHA), a member of the DEXH box helicase family of proteins, is an integral component of protein complexes that regulate transcription and splicing. The EWS-FLI1 oncoprotein is expressed as a result of the chromosomal translocation t(11;22) that occurs in patients with the Ewing's sarcoma family of tumors (ESFT). Using phage display library screening, we identified an EWS-FLI1 binding peptide containing homology to RHA. ESFT cell lines and patient tumors highly expressed RHA. GST pull-down and ELISA assays showed that EWS-FLI1 specifically bound RHA fragment amino acids 630 to 1020, which contains the peptide region discovered by phage display. Endogenous RHA was identified in a protein complex with EWS-FLI1 in ESFT cell lines. Chromatin immunoprecipitation experiments showed both EWS-FLI1 and RHA bound to EWS-FLI1 target gene promoters. RHA stimulated the transcriptional activity of EWS-FLI1 regulated promoters, including Id2, in ESFT cells. In addition, RHA expression in mouse embryonic fibroblast cells stably transfected with EWS-FLI1 enhanced the anchorage-independent phenotype above that with EWS-FLI1 alone. These results suggest that RHA interacts with EWS-FLI1 as a transcriptional cofactor to enhance its function. (Cancer Res 2006; 66(11): 5574-81)
Pulmonary sequestration: A report of an unusual case and a review of the literature
Authors: A. Blesovsky
Journal: Thorax (1967)

A case of extralobar sequestration with findings indicating a pulmonary origin is reported. The literature has been reviewed and evidence presented that intra- and extralobar sequestration are variants of the same abnormality and that the systemic artery is an associated anomaly. From the evidence available at present the pathogenesis of this anomaly is best explained as an abnormality of bronchial and foregut budding resulting from failure of normal embryonic organizer control.
Age-Dependent Cut Points for Airway Hyperresponsiveness to Distinguish Asthma from Healthy Children in Methacholine Challenge Test
Authors: Ji-Won Kwon, Eun Lee, Song-I. Yang, Young-Ho Ho Jung, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So Yeon Lee, Woo Kyung Kim, Jung Yeon Shim, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2015)
Activation of human leucocyte procollagenase by rheumatoid synovial tissue culture medium.
Authors: J Wize, T Abgarowicz, E Wojtecka-Lukasik, S Ksiezny, A M Dancewicz
Journal: Annals of the Rheumatic Diseases (1975)

Production of a factor activating leucocyte procollagenase by tissue culture of rheumatoid synovium was shown. The activator was isolated, partly purified, and shown to be thermolabile, nondialysable, and had no activity toward casein, haemoglobin, histones, and PZ-peptide. The activity of the activator was partly decreased by trypsin.
Molecular Characteristics of Canine Cardiac Myosin
Authors: ROBERT J. LUCHI, EVE MARIE KRITCHER, HADLEY L. CONN
Journal: Circulation Research (1965)

Cardiac myosin was obtained from the hearts of normal dogs by conventional extraction and precipitation techniques, followed by ammonium sulfate fractionation in the presence of 2.0 M lithium chloride. The molecular characteristics of this protein preparation are presented. Cardiac myosin prepared by this technique shows less tendency than conventionally prepared solutions to denature when stored at 0 to 4°C, and has a significantly higher ATP ase activity. Comparison of canine cardiac myosin and skeletal muscle myosin, obtained under identical conditions, revealed no differences between these two proteins in their intrinsic viscosities, S 20. w , molecular weight, and UV absorbances, although ATP ase activity was lower for cardiac myosin.
Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Assessing Tumor Vascularity and Vascular Effects of Targeted Therapies in Renal Cell Carcinoma
Authors: Mark A. Rosen, Mitchell D. Schnall
Journal: Clinical Cancer Research (2007)

Abstract Traditional cross-sectional tumor imaging focuses solely on tumor morphology. With the introduction of targeted biological therapies in human trials, morphologic change may lag behind other physiologic measures of response on clinical images. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a new imaging method for assessing the physiologic state of tumor vascularity in vivo. DCE-MRI, which uses available imaging techniques and contrast agents, assays the kinetics of tumor enhancement during bolus i.v. contrast administration. Modeling of the temporal enhancement pattern yields physiologic variables related to tumor blood flow and microvessel permeability. Changes in these variables after vascular-targeted therapy can then be quantified to evaluate the tumor vascular response. As these responses may precede morphologic tumor shrinkage, DCE-MRI might serve as a noninvasive means of monitoring early tumor response to vascular-targeted therapy. Renal cell carcinoma provides an excellent model for assessing the effect on DCE-MRI in clinical trials. The vascular richness of renal tumors provides a large dynamic scale of DCE-MRI measures. Patients with disseminated renal cell carcinoma frequently present with one or several large tumors, creating an easy imaging target for DCE-MRI evaluation. Finally, renal cell carcinoma is clearly susceptible to therapies that target tumor angiogenesis. DCE-MRI can be used to monitor the vascular changes induced by such therapies. Future efforts must be directed to standardizing image acquisition and analysis techniques to quantify tumor vascular responses.
Lineage-Specific Adaptive Evolution of the Centromeric Protein CENH3 in Diploid and Allotetraploid Oryza Species
Authors: C. D. Hirsch, Y. Wu, H. Yan, J. Jiang
Journal: Molecular Biology and Evolution (2009)

Centromeres in eukaryotic species are defined by the presence of a centromere-specific histone H3 variant, CENH3. CENH3 plays a key role in recruiting other centromeric proteins; thus, it is the central component in kinetochore formation and centromere function. The CENH3 proteins in several plant and animal species were found to be under positive selection, which was hypothesized to respond to the rapid changing of the repetitive DNA sequences associated with the centromeres. Here, we report the expression and evolution of the CenH3 genes in two allotetraploid rice species as well as their representative diploid progenitor species. Both copies of the CenH3 genes were transcribed in the two allotetraploid species and showed a nonpreferential expression pattern. Contrasting positive and stabilizing selection of the CenH3 genes was associated with different diploid Oryza species. This lineage-specific adaptive evolution of CENH3 was maintained in the two allotetraploid species. Thus, we demonstrate that the allopolyploidization events did not alter the expression or evolutionary patterns of the CenH3 genes in the Oryza species.
Drug points: Burns after photodynamic therapy
Authors: S. Hettiaratchy
Journal: BMJ (2000)

Photodynamic therapy comprises a photosensitising agent, which accumulates in malignant tissue, and a light source, which activates the photosensitiser, causing it to generate highly reactive oxygen species that destroy malignant cells. Temoporfin is a second generation photosensitiser that has a shorter half life than its predecessors and is thought to be more selective towards tumours. These two factors should decrease the incidence of photosensitivity, one of the main side effects …
De Morgan's Spots
Authors: F. P. Weber
Journal: BMJ (1947)

MDICLJURAL the total population it will show that each pers'on gets 2,900 calories per day, but of cours'e this gives a wholly'wrong'in- terpretation of the facts, since those who can eat in restaurants must consume more calories than those who cannot afford to do so.Many of my national health insurance patients cannot afford to purchase meals in restaurants, and, as Lord Cherwell has so wittily pointed out, these unfortunate people will haVe to consume either 100 oz.'(2.8 kg.) of fish, or 5 lb.(2.2 kg.) of potatoes, or 200 oz.(5.7 kg.) of cabbage in order to make up a deficient 1,300 calories.This is a gargantuan task which'is beyond the ability of any patientf'I have at the present moment.-Iam, etc.,
Enhancing the Outcome of Cell Therapy for Cardiac Repair
Authors: Emmanouil Chavakis, Masamichi Koyanagi, Stefanie Dimmeler
Journal: Circulation (2010)

C ell therapy has emerged as a promising option to treat myocardial infarction or heart failure; more than 1500 patients with cardiovascular diseases are treated with adult progenitor cells worldwide.The treatment of acute and chronic myocardial infarction with adult bone marrowderived cells provided a modest benefit in most but not all studies.A number of plausible reasons have been discussed to explain the modest effects, sending researchers back to the bench to elucidate strategies to overcome the limitations of cell therapy and to develop more efficient approaches.Such strategies include the use of other sources to isolate adult progenitor cells (eg, adipose or cardiac tissue) or the generation of pluripotent cells by the reprogramming of somatic cell types.Successful cardiac cell therapy in clinical practice also depends on the efficient delivery and the appropriate integration and alignment of injected or infused cells.The pretreatment of cells with activators to augment cell homing and survival or the improvement of cell delivery tools may provide an opportunity to increase the number of active cells in ischemic or diseased tissues, thereby increasing their therapeutic potential.Finally, the identification of molecules guiding cardiac differentiation provides novel tools to enforce the formation of new functionally active cardiomyocytes to augment cardiac regeneration in its pure sense.
Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation
Authors: Jianwen Wei, Mathieu Ferron, Christopher J. Clarke, Yusuf A. Hannun, Hongfeng Jiang, William S. Blaner, Gerard Karsenty
Journal: Journal of Clinical Investigation (2014)

Insulin signaling in osteoblasts has been shown recently to contribute to whole-body glucose homeostasis in animals fed a normal diet; however, it is unknown whether bone contributes to the insulin resistance that develops in animals challenged by a high-fat diet (HFD). Here, we evaluated the consequences of osteoblast-specific overexpression of or loss of insulin receptor in HFD-fed mice. We determined that the severity of glucose intolerance and insulin resistance that mice develop when fed a HFD is in part a consequence of osteoblast-dependent insulin resistance. Insulin resistance in osteoblasts led to a decrease in circulating levels of the active form of osteocalcin, thereby decreasing insulin sensitivity in skeletal muscle. Insulin resistance developed in osteoblasts as the result of increased levels of free saturated fatty acids, which promote insulin receptor ubiquitination and subsequent degradation. Together, these results underscore the involvement of bone, among other tissues, in the disruption of whole-body glucose homeostasis resulting from a HFD and the involvement of insulin and osteocalcin cross-talk in glucose intolerance. Furthermore, our data indicate that insulin resistance develops in bone as the result of lipotoxicity-associated loss of insulin receptors.
Vitamin K for neonates: the controversy
Authors: G Draper, A McNinch
Journal: BMJ (1994)

<h3>Objective</h3> This study aimed to explore how new family medicine graduates who want to include obstetrics in their scope of practice identify and select jobs and to understand how employment influences scope of practice in family medicine, particularly the ability to provide maternity care and deliver babies. <h3>Design</h3> Mixed-methods study including a survey and qualitative interviews conducted in 2017. <h3>Setting</h3> We electronically surveyed US family physicians and followed up with a purposeful subsample of these physicians to conduct in-depth, semistructured telephone interviews. <h3>Participants</h3> 1016 US family medicine residency graduates 2014–2016 who indicated that they intended to deliver babies in practice completed a survey; 56 of these were interviewed. <h3>Main outcome measures</h3> The survey measured the reasons for not doing obstetrics as a family physician. To identify themes regarding finding family medicine jobs with obstetrics, we used a team-based, immersion–crystallisation approach to analyse the transcribed qualitative interviews. <h3>Results</h3> Survey results (49% response rate) showed that not finding a job that included obstetrics was the primary reason newly graduated family physicians who intended to do obstetrics were not doing so. Qualitative interviews revealed that family physicians often find jobs with obstetrics through connections or recruitment efforts and make job decisions based on personal considerations such as included geographical preferences, family obligations and lifestyle. However, job-seeking and job-taking decisions are constrained by employment-related issues such as job structure, practice characteristics and lack of availability of family medicine jobs with obstetrics. <h3>Conclusions</h3> While personal reasons drove job selection for most physicians, their choices were constrained by multiple factors beyond their control, particularly availability of family medicine jobs allowing obstetrics. The shift from physician as practice owner to physician as employee in the USA has implications for job-seeking behaviours of newly graduating medical residents as well as for access to healthcare services by patients; understanding how employment influences scope of practice in family medicine can provide insight into how to support family physicians to maintain the scope of practice they desire and are trained to provide, thus, ensuring that families have access to care.