tbuckley/cabot-search huggingface dataset:
Effective glycaemic control critically determines insulin cardioprotection against ischaemia/reperfusion injury in anaesthetized dogs
Authors: Qiujun Yu, Ning Zhou, Ying Nan, Lihua Zhang, Yan Li, Xiaoke Hao, Lize Xiong, Wayne Bond Lau, Xin L. Ma, Haichang Wang, Feng Gao
Journal: Cardiovascular Research (2014)

Experimental evidence has shown significant cardioprotective effects of insulin, whereas clinical trials produced mixed results without valid explanations. This study was designed to examine the effect of hyperglycaemia on insulin cardioprotective action in a preclinical large animal model of myocardial ischaemia/reperfusion (MI/R). Anaesthetized dogs were subjected to MI/R (30 min/4 h) and randomized to normal plasma insulin/euglycaemia (NI/NG), normal-insulin/hyperglycaemia (NI/HG), high-insulin/euglycaemia (HI/NG), and high-insulin/hyperglycaemia (HI/HG) achieved by controlled glucose/insulin infusion. Endogenous insulin production was abolished by peripancreatic vessel ligation. Compared with the control animals (NI/NG), hyperglycaemia (NI/HG) significantly aggravated MI/R injury. Insulin elevation at clamped euglycaemia (HI/NG) protected against MI/R injury as evidenced by reduced infarct size, decreased necrosis and apoptosis, and alleviated inflammatory and oxidative stress (leucocyte infiltration, myeloperoxidase, and malondialdehyde levels). However, these cardioprotective effects of insulin were markedly blunted in hyperglycaemic animals (HI/HG). In vitro mechanistic study in neonatal rat cardiomyocytes revealed that insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and Akt was significantly attenuated by high glucose, accompanied by markedly increased IRS-1 O-GlcNAc glycosylation following hypoxia/reoxygenation. Inhibition of hexosamine biosynthesis with 6-diazo-5-oxonorleucine abrogated high glucose-induced O-GlcNAc modification and inactivation of IRS-1/Akt as well as cell injury. Our results, derived from a canine model of MI/R, demonstrate that hyperglycaemia blunts insulin protection against MI/R injury via hyperglycaemia-induced glycosylation and subsequent inactivation of insulin-signalling proteins. Our findings suggest that prevention of hyperglycaemia is critical for achieving maximal insulin cardioprotection for the ischaemic/reperfused hearts.
Pure erythrocytosis: Reappraisal of a study of 51 cases
Authors: Y. Najean, F. Triebel, C. Dresch
Journal: American Journal of Hematology (1981)

Abstract Fifty‐one cases of pure, primary erythrocytosis were identified and followed at Hǒpital Saint‐Louis, Paris, and compared with 350 cases of polycythemia vera (PV) observed during the same period. At the initial evaluation, these cases did not differ from PV cases with respect to age, sex ratio, degree of red cell volume increase, and clinical symptoms. They did differ by the absence of splenomegaly, granulocytosis and thrombocytosis. At a late stage of evolution only a few cases developed classical criteria of PV. From this group of apparently homogeneous cases, two subgroups evolved. Sixty percent of the cases were highly responsive to myelosuppression with 32 P. The median duration of the first remission was greater than five years, the mean yearly dose of 32 P was very low, and there was a low incidence of complications. The other group (40% of cases) was relatively resistant to myelosuppressive agents. The development of better methods to investigate this disorder might help in discriminating these two groups from both an etiological and pathophysiological viewpoint. The thromboembolic risk of these diseases suggests that myelosuppressive therapy should be utilized in older patients with higher risk of vascular accidents, reserving phlebotomy for younger patients and those who are shown to be resistant to 32 P therapy.
Massive pleural effusion: an unusual presentation of Castleman's disease
Authors: SP Reynolds, AR Gibbs, R Weeks, H Adams, BH Davies
Journal: European Respiratory Journal (1992)

Giant lymph node hyperplasia (Castleman's Disease) is a rare cause of pleural effusion. We report the case of a 51 yr old West Indian male, who presented with a recurrent massive pleural effusion, due to a tumour arising from the pleura. He underwent parietal pleurectomy and subtotal excision of the tumour. Histological analysis of the specimen showed the features of multicentric Castleman's disease. Nine months following surgery he remains well, with no recurrence of the effusion.
NUTRITION AND PRE-CONCEPTION CARE
Authors: P.J. Barlow, S. Sidani, R.D. Rice, Ellen Grant, Keith Mumby, Hugh Cox, Patrick Kingsley, John Lester, Edward Hamlyn, Belinda Barnes, Pamela Tatham, John Nichols, Dorothy West, D. Bryce-Smith, N.I. Ward, Andrew Taylor, S.S. Brown, H.T. Delves, A.W. Walker, D. Baldwin, C. Toothill
Journal: The Lancet (1985)
Comparison of the effects of intravenous almitrine and positive end-expiratory pressure on pulmonary gas exchange in adult respiratory distress syndrome
Authors: JF Prost, P Desche, F Jardin, A Margairaz
Journal: European Respiratory Journal (1991)

The effects of almitrine on pulmonary gas exchange and haemodynamics were compared to those of positive end-expiratory pressure (PEEP) in 10 patients with a severe adult respiratory distress syndrome (ARDS) who required continuous mechanical ventilation. Haemodynamic and gas exchange measurements were made before and after 30 min of PEEP at a level of 10 cmH2O, then 30 min later, before and at the end of the intravenous infusion of almitrine at a dose of 0.25 mg.kg-1 in 30 min. There was no significant difference between baseline gas exchange and haemodynamic parameters. PEEP and almitrine increased Pao (p = 0.001) from 10.9 to 12.6 kPa and from 10.6 to 12.6 kPa (1 kPa = 7.5 mmHg), respectively, and ratio of venous admixture to total blood flow (Qs/Qt) decreased (p less than 0.001) from 34 to 29% and from 33 to 29%, respectively, the effects of PEEP and almitrine being not significantly different. Neither PEEP nor almitrine caused a significant change in arterial carbon dioxide tension (PaCO2). The haemodynamic parameters did not change significantly with almitrine, whereas mean systemic arterial pressure decreased from 85.4 to 81.1 mmHg (p less than 0.05) with PEEP. These results are consistent with the hypothesis that both treatments improve ventilation/perfusion (VA/Q) distributions, by an increase in functional residual capacity in the case of PEEP and a redistribution of pulmonary perfusion in the case of almitrine.
Anterior Communicating Aneurysms
Authors: J. Lawrence Pool
Journal: JAMA (1966)

Arecent communication 1 unfortunately leaves the impression that the surgical treatment of ruptured anterior communicating aneurysms might just as well be abandoned because—according to statistics in that report—No difference between the results of surgical and conservative treatment was detected, and the death-rate remained approximately the same irrespective of surgical procedure.  This statement is based on a masterful five-year survey of 300 patients who had recovered, after rupture of an anterior-communicating-artery aneurysm, and were in good or reasonably good condition at the time treatment was begun. They were classified as group B, or favorable-risk patients, in contrast to the poor-risk or comatose patients of group A. On the basis of randomized selection, approximately one half of the 300 were treated by surgery and the remainder by conservative therapy.  Conservative therapy, which consisted of bed rest for six weeks with or without hypotensive therapy, led to a mortality within six months of
Phase I Study of Cloretazine (VNP40101M), a Novel Sulfonylhydrazine Alkylating Agent, Combined with Cytarabine in Patients with Refractory Leukemia
Authors: Francis Giles, Srdan Verstovsek, Deborah Thomas, Stanton Gerson, Jorge Cortes, Stefan Faderl, Alessandra Ferrajoli, Farhad Ravandi, Steven Kornblau, Guillermo Garcia-Manero, Elias Jabbour, Susan O'Brien, Verena Karsten, Ann Cahill, Karen Yee, Maher Albitar, Mario Sznol, Hagop Kantarjian
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cloretazine (VNP40101M) is a novel sulfonylhydrazine alkylating agent with significant antileukemia activity. A phase I study of cloretazine combined with cytarabine (1-β-d-arabinofuranosylcytosine, ara-C) was conducted in patients with refractory disease. Design: Ara-C was given i.v. at a fixed dose of 1.5 gm/m2/d by continuous infusion for 4 days (patients ages &amp;lt;65 years at time of diagnosis) or 3 days (patients ages ≥65 years). Cloretazine was given i.v. over 15 to 60 minutes on day 2 at a starting dose of 200 mg/m2, with escalation in 100 mg/m2 increments in cohorts of three to six patients until a maximum tolerated dose was established. The DNA repair enzyme O6-alkylguanine DNA alkyltransferase (AGT) was measured at baseline. Results: Forty patients, including 32 with acute myeloid leukemia, received 47 courses of treatment. Complete responses were seen at cloretazine dose levels of ≥400 mg/m2 in 10 of 37 (27%) evaluable patients, and in this patient subset, AGT activity was significantly lower in patients that responded to treatment than in patients who did not (P ≤ 0.027). Dose-limiting toxicities (gastrointestinal and myelosuppression) were seen with 500 and 600 mg/m2 of cloretazine combined with the 4-day ara-C schedule but not seen with the 3-day schedule. Conclusion: The recommended cloretazine dose schedule for future studies is 600 mg/m2 combined with 1.5 gm/m2/d continuous infusion of ara-C for 3 days. The cloretazine and ara-C regimen has significant antileukemic activity. AGT activity may be a predictor of response to cloretazine.
Structural and kinetic comparison of recombinant human single- and two-chain tissue plasminogen activator.
Authors: J Loscalzo
Journal: Journal of Clinical Investigation (1988)

We examined the similarities and differences in conformation between recombinant human single-chain tissue plasminogen activator (sct-PA) and two-chain tissue plasminogen activator (tct-PA), and compared these structural data with measurement of enzymatic activity. The intrinsic protein fluorescence of native tct-PA was 54% that of sct-PA. Differences in steady state protein fluorescence were also noted with denaturation of these plasminogen activators, as well as in the quenching of intrinsic fluorescence of the reduced, alkylated species by iodide. Using the chromogenic substrate H-D-isoleucyl-L-prolyl-L-arginine-p-nitroanilide (S-2288), the catalytic efficiency of sct-PA was found to be 26% that of tct-PA, and this was primarily a reflection of the difference in Km. On addition of soluble fibrin monomer prepared with the tetrapeptide glycyl-L-prolyl-L-arginyl-L-proline (GPRP), the catalytic efficiency of both species increased by 13-fold for sct-PA and by 3.5-fold for tct-PA to approximately the same value. Using the fluorophore eosin iodoacetamide covalently coupled to the single free cysteine in the molecule, Cys 83, the microenvironment of the fibrin-binding site located near this residue was studied. On addition of soluble fibrin monomer to eosin-labeled tct-PA, no effect on eosin fluorescence was noted. Eosin-labeled tct-PA had 16% less eosin fluorescence than did sct-PA and on addition of soluble fibrin monomer to eosin-labeled sct-PA, a decrease in eosin fluorescence, approaching that of eosin coupled to tct-PA, was observed. Together, these structural and kinetic data suggest that sct-PA undergoes a conformational change on binding to fibrin monomer that leads to dramatic differences in catalytic efficiency of the single-chain species. In so doing, sct-PA bound to fibrin assumes the kinetic profile of tct-PA bound to fibrin.
Effect of Ujjayi and Bhastrika Pranayama on selected physiological variables of physically challenged students
Authors: Indu Mazumdar, Avinash Suryavanshi
Journal: British Journal of Sports Medicine (2010)

The purpose of the study was to analyse the effect of Ujjayi and Bhastrika Pranayama on selected physiological variables. For this 60 physically challenged male students were randomly selected as the subjects from Amar Jyoti School and Roshni Rehabilitation Centre, Gwalior. Further the subjects were divided into two groups that is, experimental group and control group. The experimental group followed of Ujjayi and Bhastrika Pranayama for a period of 6 weeks. The training was given for 5 days in a week in the morning. Only four physiological variables that is, vital capacity, positive breath holding time, resting pulse rate and blood pressure were selected for the study. Pre- and post-test data on selected physiological variables were recorded prior to and after completion of 6 weeks pranayama training of experimental group, and the control group did not participate in the training programme. The criterion measures for measuring vital capacity was measured with Recorder and Medicare Systems Spirometer (Helios 401) in litres, positive breath holding and resting pulse rate was measured with the help of stopwatch, and blood pressure was measured by sphygmomanometer and stethoscope. Paired ‘t’ test statistical technique was employed to analyse the raw data, and the mean difference between the pretest and post-test scores each of the criterion variables of the groups. The level of significance was chosen at 0.05 level. From the findings it was observed that ‘t’ ratio was not significant in case of resting pulse rate and diastolic blood pressure. However in case of vital capacity and positive breath holding time ‘t’ was significant.
Universal features in the genome-level evolution of protein domains
Authors: Marco Cosentino Lagomarsino, Alessandro L Sellerio, Philip D Heijning, Bruno Bassetti
Journal: Genome biology (2009)

Protein domains can be used to study proteome evolution at a coarse scale. In particular, they are found on genomes with notable statistical distributions. It is known that the distribution of domains with a given topology follows a power law. We focus on a further aspect: these distributions, and the number of distinct topologies, follow collective trends, or scaling laws, depending on the total number of domains only, and not on genome-specific features.We present a stochastic duplication/innovation model, in the class of the so-called 'Chinese restaurant processes', that explains this observation with two universal parameters, representing a minimal number of domains and the relative weight of innovation to duplication. Furthermore, we study a model variant where new topologies are related to occurrence in genomic data, accounting for fold specificity.Both models have general quantitative agreement with data from hundreds of genomes, which indicates that the domains of a genome are built with a combination of specificity and robust self-organizing phenomena. The latter are related to the basic evolutionary 'moves' of duplication and innovation, and give rise to the observed scaling laws, a priori of the specific evolutionary history of a genome. We interpret this as the concurrent effect of neutral and selective drives, which increase duplication and decrease innovation in larger and more complex genomes. The validity of our model would imply that the empirical observation of a small number of folds in nature may be a consequence of their evolution.
Virginia Apgar and the Apgar Score: Kudos and a Correction
Authors: L. Joseph Butterfield
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The captivating collage by Mr Skolnick on Dr Virginia Apgar<sup>1</sup>included the history of the Apgar Memorial String Quartet, the beguiling personality of Dr Virginia Apgar, and that incredible 1957 nocturnal caper at the Harkness Pavillion when she and Carleen Hutchins "liberated" the curly maple shelf of a telephone booth that they transposed to the back of Apgar's viola. It is an unfortunate gaffe, however, that the article claims that the Apgar score "is often highly predictive of the child's later psychocognitive development" to those who would retire or defend the Apgar score. This issue has been debated ad nauseum with the usual conclusion that the Apgar score is still the best clinical tool for the evaluation of the newly born infant and that it was never intended to predict later outcome.<sup>2</sup>
TL1A Both Promotes and Protects from Renal Inflammation and Injury
Authors: Rafia S. Al-Lamki, Jun Wang, Aviva M. Tolkovsky, J. Andrew Bradley, Jules L. Griffin, Sathia Thiru, Eddie C.Y. Wang, Eleanor Bolton, Wang Min, Paul Moore, Jordan S. Pober, John R. Bradley
Journal: Journal of the American Society of Nephrology (2008)

Death receptor 3 (DR3), a member of the TNF receptor (TNFR) superfamily, is induced in human renal tubular epithelial cells (TEC) in response to injury. This study examined the expression and actions of TL1A, the principal ligand for DR3. In histologically normal tissue from biopsy or nephrectomy specimens of renal allografts, TL1A mRNA and protein were expressed in vascular endothelial cells but not in TEC. In specimens of acute or antibody-mediated allograft rejection, vascular endothelial cells and infiltrating leukocytes expressed increased TL1A mRNA and protein, but TEC expressed TL1A protein without mRNA, consistent with uptake of exogenous ligand. Addition of TL1A to organ cultures of human or mouse kidney caused activation of NF-κB, expression of TNFR2, activation of caspase-3, and apoptosis in TEC. Inhibition of NF-κB activation increased TL1A-mediated caspase-3 activation and apoptosis of TEC, but it did not reduce the induction of TNFR2. In organ culture of DR3-deficient mouse kidneys, addition of TL1A induced TNFR2 but did not activate NF-κB and did not increase apoptosis of TEC. These data suggest that TL1A may contribute to renal inflammation and injury through DR3-mediated activation of NF-κB and caspase-3, respectively, but that an unidentified receptor may mediate the NF-κB–independent induction of TNFR2 in TEC.
Major histocompatibility complex-restricted antigen receptor on T cells. VIII. Role of the LFA-1 molecule.
Authors: W T Golde, J W Kappler, J Greenstein, B Malissen, L Hood, P Marrack
Journal: The Journal of Experimental Medicine (1985)

We show that the LFA-1 molecule on T cells does not play a role in the stimulation of T cell hybridomas by certain targets, namely antigen presented by L cell derivatives or polyvalent anti-receptor antibody. These results suggest that LFA-1 may act by binding to ligands that are not present on all cells. We hope this result will help us and others to establish the true role of LFA-1 in T cell responses.
From Access to Evidence: An Advocate’s Journey
Authors: Musa Mayer
Journal: Journal of Clinical Oncology (2003)

Article Tools ART OF ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.07.217 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 14551309 From Access to Evidence: An Advocate’s Journey Musa MayerxMusa MayerSearch for articles by this author https://doi.org/10.1200/JCO.2003.07.217 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition
Authors: Koichi Kaikita, Agnes B. Fogo, Lijun Ma, John A. Schoenhard, Nancy J. Brown, Douglas E. Vaughan
Journal: Circulation (2001)

Background Long-term inhibition of nitric oxide synthase (NOS) is known to induce hypertension and perivascular fibrosis. Recent evidence also suggests that long-term NOS inhibition induces expression of plasminogen activator inhibitor-1 (PAI-1) in vascular tissues and that PAI-1 may contribute to the development of fibrosis after chemical or ionizing injury. On the basis of these observations, we hypothesized that PAI-1 may influence the vascular response to long-term NOS inhibition by N ω -nitro- l -arginine methyl ester (L-NAME). Methods and Results We compared the temporal changes in systolic blood pressure and coronary perivascular fibrosis in PAI-1–deficient (PAI-1 −/− ) and wild-type (WT) male mice (N=6 per group). At baseline, there were no significant differences in blood pressure between groups. After initiation of L-NAME, systolic blood pressure increased in both groups at 2 weeks. Over an 8-week study period, systolic blood pressure increased to 141±3 mm Hg in WT animals versus 112±4 mm Hg in PAI-1 −/− mice ( P &lt;0.0001). The extent of coronary perivascular fibrosis increased significantly in L-NAME–treated WT mice ( P &lt;0.01 versus PAI-1 −/− mice). Cardiac type I collagen mRNA expression was greater in control ( P &lt;0.01) and L-NAME–treated PAI-1 −/− ( P &lt;0.05) groups than in control WT mice, indicating that PAI-1 deficiency prevents the increase of collagen deposition by promoting matrix degradation. Conclusions These findings suggest that PAI-1 deficiency alone is sufficient to protect against the structural vascular changes that accompany hypertension in the setting of long-term NOS inhibition. Direct inhibition of vascular PAI-1 activity may provide a new therapeutic strategy for the prevention of arteriosclerotic cardiovascular disease.
Antibody-Specific Model of Amino Acid Substitution for Immunological Inferences from Alignments of Antibody Sequences
Authors: Alexander Mirsky, Linda Kazandjian, Maria Anisimova
Journal: Molecular Biology and Evolution (2014)

Antibodies are glycoproteins produced by the immune system as a dynamically adaptive line of defense against invading pathogens. Very elegant and specific mutational mechanisms allow B lymphocytes to produce a large and diversified repertoire of antibodies, which is modified and enhanced throughout all adulthood. One of these mechanisms is somatic hypermutation, which stochastically mutates nucleotides in the antibody genes, forming new sequences with different properties and, eventually, higher affinity and selectivity to the pathogenic target. As somatic hypermutation involves fast mutation of antibody sequences, this process can be described using a Markov substitution model of molecular evolution. Here, using large sets of antibody sequences from mice and humans, we infer an empirical amino acid substitution model AB, which is specific to antibody sequences. Compared with existing general amino acid models, we show that the AB model provides significantly better description for the somatic evolution of mice and human antibody sequences, as demonstrated on large next generation sequencing (NGS) antibody data. General amino acid models are reflective of conservation at the protein level due to functional constraints, with most frequent amino acids exchanges taking place between residues with the same or similar physicochemical properties. In contrast, within the variable part of antibody sequences we observed an elevated frequency of exchanges between amino acids with distinct physicochemical properties. This is indicative of a sui generis mutational mechanism, specific to antibody somatic hypermutation. We illustrate this property of antibody sequences by a comparative analysis of the network modularity implied by the AB model and general amino acid substitution models. We recommend using the new model for computational studies of antibody sequence maturation, including inference of alignments and phylogenetic trees describing antibody somatic hypermutation in large NGS data sets. The AB model is implemented in the open-source software CodonPhyML (http://sourceforge.net/projects/codonphyml) and can be downloaded and supplied by the user to ProGraphMSA (http://sourceforge.net/projects/prographmsa) or other alignment and phylogeny reconstruction programs that allow for user-defined substitution models.