tbuckley/cabot-search huggingface dataset:
Disproportional Plastome-Wide Increase of Substitution Rates and Relaxed Purifying Selection in Genes of Carnivorous Lentibulariaceae
Authors: Susann Wicke, Bastian Schäferhoff, Claude W. dePamphilis, Kai F. Müller
Journal: Molecular Biology and Evolution (2013)

Carnivorous Lentibulariaceae exhibit the most sophisticated implementation of the carnivorous syndrome in plants. Their unusual lifestyle coincides with distinct genomic peculiarities such as the smallest angiosperm nuclear genomes and extremely high nucleotide substitution rates across all genomic compartments. Here, we report the complete plastid genomes from each of the three genera Pinguicula, Utricularia, and Genlisea, and investigate plastome-wide changes in their molecular evolution as the carnivorous syndrome unfolds. We observe a size reduction by up to 9% mostly due to the independent loss of genes for the plastid NAD(P)H dehydrogenase and altered proportions of plastid repeat DNA, as well as a significant plastome-wide increase of substitution rates and microstructural changes. Protein-coding genes across all gene classes show a disproportional elevation of nonsynonymous substitutions, particularly in Utricularia and Genlisea. Significant relaxation of purifying selection relative to noncarnivores occurs in the plastid-encoded fraction of the photosynthesis ATP synthase complex, the photosystem I, and in several other photosynthesis and metabolic genes. Shifts in selective regimes also affect housekeeping genes including the plastid-encoded polymerase, for which evidence for relaxed purifying selection was found once during the transition to carnivory, and a second time during the diversification of the family. Lentibulariaceae significantly exhibit enhanced rates of nucleotide substitution in most of the 130 noncoding regions. Various factors may underlie the observed patterns of relaxation of purifying selection and substitution rate increases, such as reduced net photosynthesis rates, alternative paths of nutrient uptake (including organic carbon), and impaired DNA repair mechanisms.
Common Protective and Diverse Smooth Muscle Cell Effects of AAV-Mediated Angiopoietin-1 and -2 Expression in Rat Cardiac Allograft Vasculopathy
Authors: Antti I. Nykänen, Katri Pajusola, Rainer Krebs, Mikko A.I. Keränen, Olivier Raisky, Petri K. Koskinen, Kari Alitalo, Karl B. Lemström
Journal: Circulation Research (2006)

Angiopoietin-1 (Ang1) and Ang2 regulate the maintenance of normal vasculature by direct endothelial and indirect smooth muscle cell (SMC) effects. Dysfunction of vascular wall cells is considered central in cardiac allograft vasculopathy (CAV), where inflammation and arterial injury initiate subsequent intimal SMC proliferation. In this study, we investigated the effect of exogenous Ang1 and Ang2 in chronically rejecting rat cardiac allografts by intracoronary adeno-associated virus (AAV)-mediated gene transfer. Bioluminescent imaging of AAV-transfected syngeneic grafts revealed gradual and stable transgene expression in graft cardiomyocytes. In cardiac allografts, both AAV-Ang1 and AAV-Ang2 decreased inflammation and increased antiapoptotic Bcl-2 mRNA and Bcl-2/Bax ratio at 8 weeks. Only AAV-Ang2 decreased the development of CAV, whereas AAV-Ang1 activated arterial SMC and increased PDGF-A mRNA in the allograft. Collectively, our results show that exogenous Ang1 and Ang2 have similar antiinflammatory and antiapoptotic effects in cardiac allografts. Prolonged AAV-mediated Ang1 transgene expression also induced SMC activation, whereas AAV-Ang2 lacked the SMC activating effects and decreased CAV. Our results thus highlight the common protective and diverse SMC effects of Ang1 and Ang2 in cardiac allograft microenvironment and the importance of timing of angiopoietins to achieve therapeutic effects.
Suppression of ventricular arrhythmias by propafenone, a new antiarrhythmic agent, during acute myocardial infarction in the conscious dog. A comparative study with lidocaine.
Authors: H S Karagueuzian, T Fujimoto, T Katoh, T Peter, A McCullen, W J Mandel
Journal: Circulation (1982)

The responsiveness of ventricular tachycardia (VT) to propafenone, a new antiarrhythmic agent, was evaluated in the conscious dog during acute myocardial infarction (AMI).AMI was produced in the anesthetized closed-chest dogs with an intracoronary catheter system by permanent occlusion in eight dogs and by 2-hour occlusion followed by reperfusion of the left anterior descending coronary artery in eight others.Twenty-four hours after surgery, all dogs in both groups had VTwith similar characteristics (rates of 130-220 beats/min) in the conscious, nonsedated state.Administration of propafenone, 4 mg/kg i.v. over 2 minutes, immediately and completely suppressed VT in seven of the permanently occluded and in all eight dogs in the reperfused group.The duration of propafenone-induced normal sinus rhythm (NSR) was inversely related to the rate of VT.Intravenous infusion of propafenone, 0.2 mg/kg/min, after a 4-mg/kg i.v.bolus maintained NSR for the duration of infusion.Propafenone did not change the mean blood pressure.Lidocaine, as much as 5 mg/kg i.v., was ineffective when the VT rate was greater than 160 beats/min and restored NSR only transiently (3-6 minutes) when the VT rate was less than 160 beats/min in either group (p < 0.001 compared with propafenone).Propafenone, unlike lidocaine, significantly (p < 0.05) increased both cathodal and bipolar diastolic excitability threshold and shifted upward the tail portion of the strength-interval relation of the right ventricle.Propafenone had no effect on the effective refractory period of the right ventricle.Plasma propafenone levels during propafenone-induced NSR and myocardial excit- ability measurements were 3.2 1.6 gg/ml in the reperfused group and 3.0 1.68 ,tg/ml in the perma- nently occluded group (mean ± SD) (p > 0.1).We conclude that propafenone is very effective against VT during AMI in the dog, and it may be effective in lidocaine-resistant VT during acute ischemia.
On the Action of the Bronchial Muscles
Authors: C. R. Hall
Journal: BMJ (1861)

held under such pleasant circumstances, I shall notice it, with a very short allusion to the antecedent.That some surgeons would operate in such a case as the above, I am well aware; but, most assuredly, a very large majority would not; and I beg to say, as a last remark, that I am not attempting to lay down any new doctrine, but merely desire to draw more general attention to this one particular, that very undoubted, considerable, and peculiar advantages, may be conferred by an operation on the victim of cancer, even after the ulcerative stage is established.
Adverse Event Reporting in Cancer Clinical Trial Publications
Authors: Shanthi Sivendran, Asma Latif, Russell B. McBride, Kristian D. Stensland, Juan Wisnivesky, Lindsay Haines, William K. Oh, Matthew D. Galsky
Journal: Journal of Clinical Oncology (2013)

Reporting adverse events is a critical element of a clinical trial publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT) group generated recommendations regarding the appropriate reporting of adverse events. The degree to which these recommendations are followed in oncology publications has not been comprehensively evaluated.A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified eligible randomized, controlled phase III trials in metastatic solid malignancies. Publications were assessed for 14 adverse event-reporting elements derived from the CONSORT harms extension statement; a completeness score (range, 0 to 14) was calculated by adding the number of elements reported. Linear regression analysis identified which publication characteristics associated with reporting completeness.A total of 175 publications, with data for 96,125 patients, were included in the analysis. The median completeness score was eight (range, three to 12). Most publications (96%) reported only adverse events occurring above a threshold rate or severity, 37% did not specify the criteria used to select which adverse events were reported, and 88% grouped together adverse events of varying severity. Regression analysis revealed that trials without a stated funding source and with an earlier year of publication had significantly lower completeness scores.Reporting of adverse events in oncology publications of randomized trials is suboptimal and characterized by substantial selectivity and heterogeneity. The development of oncology-specific standards for adverse event reporting should be established to ensure consistency and provide critical information required for medical decision-making.
Combat-related posttraumatic stress disorder among second-generation Holocaust survivors: preliminary findings
Authors: Z Solomon, M Kotler, M Mikulincer
Journal: American Journal of Psychiatry (1988)

The authors assessed the impact of the Nazi Holocaust on the course and symptoms of posttraumatic stress disorder (PTSD) among Israeli combat stress reaction casualties. They examined a sample of 96 such casualties of the 1982 Lebanon War whose parents had gone through the Nazi Holocaust and compared them to casualties who did not have such family history for 3 consecutive years beginning 1 year after their participation in the war. Results showed that 2 and 3 years after their participation in the 1982 Lebanon War, the children of Holocaust survivors, i.e., "second-generation" casualties, had higher rates of PTSD than did the control subjects, as well as a somewhat different clinical picture. Clinical and methodological implications of the findings are discussed.
Metabolic clearance and production rates of human growth hormone
Authors: Andrew L. Taylor, Joseph L. Finster, Daniel H. Mintz
Journal: Journal of Clinical Investigation (1969)

The metabolic clearance rate (MCR) of human growth hormone (HGH) was determined by the constant infusion to equilibrium technique utilizing HGH-(125)I. 22 control subjects had a MCR of 229 +/-52 ml/min (mean +/-SD). No difference was evident between sexes, or between various age groups. Patients with acromegaly demonstrated normal MCR's. Moreover, acute elevations of plasma growth hormone concentrations in normal subjects did not alter the MCR of HGH. The MCR was relatively constant from day to day and within the day when subjects were evaluated in the supine position. In contrast, the assumption of the upright position was associated with a mean 24% decrease in the MCR. These results were contrasted with the MCR of HGH observed in a small number of patients with altered thyroid function or diabetes mellitus. In six patients with hypothyroidism the MCR (131 +/-36 ml/min) was significantly decreased (P < 0.001); whereas the MCR in eight patients with hyperthyroidism (240 +/-57 ml/min) did not differ from control subjects. The MCR in eight patients with insulin-independent diabetes mellitus (IID) (185 +/-41 ml/min) and in eight patients with insulin-dependent diabetes mellitus (IDD) (136 +/-31 ml/min) were significantly different from control subjects (P = < 0.05 and P = < 0.001, respectively). These data were interpreted to indicate that the plasma HGH-removing mechanism(s) is not saturated at physiologic plasma HGH levels, that plasma HGH levels alone may not permit distinction between variations in pituitary release of the hormone and its rate of clearance from the plasma, and that the estimation of the MCR of HGH may help clarify the mechanism of abnormal plasma HGH responses to various stimuli. Production rates of HGH (PR) in control subjects (347 +/-173 mmug/min) were contrasted with hyperthyroid patients (529 +/-242 mmug/min, P < 0.05), hypothyroid patients (160 +/-69 mmug/min, P < 0.02), IID (245 +/-100 mmug/min, NS), and IDD (363 +/-153 mmug/min, NS). Considerable variability in the determination of the concentrations of immunoprecipitable HGH-(125)I and endogenous plasma HGH concentrations was encountered at apparent equilibrium conditions. Since both factors are necessary for the PR calculations, the wide 95% confidence limits of the PR's did not permit a clear interpretation of the significance of these observations.
IL-25 Induces M2 Macrophages and Reduces Renal Injury in Proteinuric Kidney Disease
Authors: Qi Cao, Changqi Wang, Dong Zheng, Ya Wang, Vincent W. S. Lee, Yuan Min Wang, Guoping Zheng, Thian Kui Tan, Di Yu, Stephen I. Alexander, David C. H. Harris, Yiping Wang
Journal: Journal of the American Society of Nephrology (2011)

The kidney contains receptors for the cytokine IL-25, but the effects of IL-25 in CKD are unknown. Here, we induced adriamycin nephropathy in both BALB/c mice and severe combined immunodeficient (SCID) mice, and we injected IL-25 for 7 consecutive days starting at day 5 after adriamycin administration. BALB/c mice treated with IL-25 had less glomerulosclerosis, tubular atrophy, interstitial expansion, and proteinuria than control mice at day 28. IL-25 increased the levels of IL-4 and IL-13 in serum, kidney, renal draining lymph nodes, and CD4+ lymphocytes. IL-25 also directly suppressed effector macrophages in vitro and in vivo and induced alternatively activated (M2) macrophages in vivo. However, in SCID mice and in BALB/c mice treated with IL-4/13–neutralizing antibody, IL-25 failed to protect against renal injury and did not induce M2. In conclusion, IL-25 protects against renal injury in adriamycin nephropathy in mice by, at least in part, inducing Th2 immune responses.
Proapoptotic Fas Ligand Is Expressed by Normal Kidney Tubular Epithelium and Injured Glomeruli
Authors: CORINA LORZ, ALBERTO ORTIZ, PILAR JUSTO, SILVIA GONZÁLEZ-CUADRADO, NATALIA DUQUE, CARMEN GÓMEZ-GUERRERO, JESÚS EGIDO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Fas ligand (FasL) is a cell membrane cytokine that can promote apoptosis through activation of Fas receptors. Fas receptor activation induces glomerular cell apoptosis in vivo and participates in tubular cell death during acute renal failure. However, there is little information on the expression of FasL in the kidney. This study reports that FasL mRNA and protein are present in normal mouse and rat kidney. In situ hybridization and immunohistochemistry showed that proximal tubular epithelium is the main site of FasL expression in the normal kidney. In addition, increased total kidney FasL mRNA and de novo FasL protein expression by glomerular cells were observed in two different models of glomerular injury: rat immune-complex proliferative glumerulonephritis and murine lupus nephritis. Both full-length and soluble FasL were increased in the kidneys of the mice with nephritis. Cultured murine proximal tubular epithelial MCT cells and primary cultures of murine tubular epithelial cells expressed FasL mRNA and protein. Tubular epithelium-derived FasL induced apoptosis in Fassensitive lymphoid cell lines but not in Fas-resistant lymphoid cell lines. By contrast, MCT cells grown in the presence of the survival factors of serum were resistant to FasL, and only became partially sensitive to apoptosis induced by high concentrations (100 ng/ml) of FasL upon serum deprivation. However, MCT cells stimulated with inflammatory mediators (tumor necrosis factor-α, interferon-γ, and lipopolysaccharide) increased cell surface Fas expression and were sensitized to apoptosis induced by FasL (FasL 55 ± 5% versus control 8.3 ± 4.1% apoptotic cells at 24 h, P &lt; 0.05). Cytokine-primed primary cultures of tubular epithelial cells also acquired sensitivity to FasL-induced apoptosis. These results suggest that FasL expression by intrinsic renal cells may play a role in cell homeostasis in the normal kidney and during renal injury.
Localized Bilharzial Granuloma of the Lung Simulating a Tumour
Authors: S. H. El Mallah, M. Hashem
Journal: Thorax (1953)

The diagnosis of solitary, circumscribed lung shadows is one of the most difficult problems in thoracic surgery.Many of these cases are asymptomatic and are detected by mass radiography.The long list of conditions that lead to these shadows, and the fact that they share, to a great extent, the same signs and symptoms, show how difficult it may be to reach a definite diagnosis.Husfeldt and Carlsen (1950) stated that they had had to do thoracotomics on 33 occasions in order to diagnose such cases.It is not the intention of this paper to discuss the differential diagnosis of such shadows, but to report an unusual case.One of us (S.H. M.) came across a patient with symptoms presenting mainly as a solitary lung shadow.Every possible method of investigation failed to clarify the diagnosis.Exploratory thoraco- tomy was therefore carried out, and, as the condition was judged to be carcinoma at operation, pneu- monectomy was performed.On pathological examination of the specimen it turned out to be a case of bilharzia.To our knowledge a case of this type has not been reported before. CASE REPORTB. A. was a man aged 47 years who worked as a farmer and was seen in the Out-patient Department on1 December 31, 1950, complaining of pain in the right sid& of the chest accompanied by cough and slight
Mechanisms of Inhibition of Heart Rate by Phenylephrine
Authors: SARLA VARMA, S. D. JOHNSEN, D. E. SHERMAN, W. B. YOUMANS
Journal: Circulation Research (1960)

Studies were performed to determine the effects of phenylephrine in dogs under chloralose as influenced by mechanical buffering of blood pressure, adrenergic blockade produced by injection of phenoxybenzamine, and combination of the mechanical buffering of blood pressure and phenoxybenzamine administration. Chloralose did not interfere with and possibly mildly sensitized the cardioinhibitory response to phenylephrine. Tachyphylaxis did not occur when moderate doses of phenylephrine were injected at intervals of not less than 15 minutes. Either mechanical buffering or administration of phenoxybenzamine partially prevented the pressor response to phenylephrine, and the cardioinhibitory response correspondingly was less. When the increase in blood pressure was prevented entirely by mechanical buffering of blood pressure combined with phenoxybenzamine administration, phenylephrine caused either no change in heart rate or a mild acceleration. It is concluded that the decreases in heart rate which are observed following injection of phenylephrine, in the doses used in this study, are secondary to the adrenergic actions of the compound.
Salusin-β in paraventricular nucleus increases blood pressure and sympathetic outflow via vasopressin in hypertensive rats
Authors: Wei-Wei Chen, Hai-Jian Sun, Feng Zhang, Ye-bo Zhou, Xiao-Qing Xiong, Jue-Jin Wang, Guo-Qing Zhu
Journal: Cardiovascular Research (2013)

Salusin-β is a bioactive peptide with peripheral hypotensive, mitogenic and pro-atherosclerotic effects. The present study was designed to determine the roles of salusin-β in the paraventricular nucleus (PVN) and its relationship with arginine vasopressin (AVP) in hypertension and sympathetic activation.Renovascular hypertension was induced by two-kidney, one-clip (2K1C) in male Sprague-Dawley rats. Acute experiments were carried out 4 weeks after 2K1C or sham-operation under urethane and alpha-chloralose anaesthesia. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded. Microinjection of salusin-β into the PVN increased the RSNA, MAP, and HR in a dose-related manner, whereas anti-salusin-β IgG in the PVN decreased the RSNA and MAP, and abolished the effects of salusin-β in 2K1C rats. However, either salusin-β or anti-salusin-β IgG in the PVN failed to cause any significant effects in sham-operated rats. The number of salusin-β-like immunopositive neurons in the PVN was significantly increased in 2K1C rats. Salusin-β in the PVN increased the plasma AVP and norepinephrine levels in 2K1C rats, but not in sham-operated rats. Iv injection of dTyr(CH2)5(Me)AVP (an AVP V1-receptor antagonist, AAVP) decreased RSNA and MAP, and abolished the effects of salusin-β in the PVN in 2K1C rats. Microinjection of AAVP into the rostral ventrolateral medulla (RVLM), but not into the PVN, abolished the effects of salusin-β on RSNA and HR.Salusin-β in the PVN increases blood pressure, heart rate, and sympathetic outflow via both circulating AVP and AVP in the RVLM in hypertensive rats.
Does antidepressant medication in patients with hepatitis C undergoing interferon treatment reduce therapeutic efficacy?
Authors: G Robaeys, M C Wichers, J De Bie, G H Koek, F Buntinx, J Van Os
Journal: Gut (2008)

Activation of the inflammatory immune system, as evidenced by the effects of interferon α (IFNα) treatment, induces depressive symptoms. Prescription of a selective serotonin reuptake inhibitor (SSRI) is now advocated in combination with antiviral therapy in patients exposed to IFNα when early symptoms of depression emerge. The recently published article written by Kraus et al ( Gut 2008; 57 :531–6) gives further evidence for the efficacy of SSRIs to treat depressive symptoms during IFNα treatment.

The mechanisms by which SSRIs reduce depressive symptoms remain unclear. Several hypotheses, such as impact on serotonin activity or neurotrophic actions, have been proposed. Another, that has good face validity in this context, is that the anti-inflammatory properties of SSRIs mediate at least in part the decrease in depressive symptoms. Antidepressants have been shown in …
HDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events
Authors: Philip Barter, Antonio M. Gotto, John C. LaRosa, Jaman Maroni, Michael Szarek, Scott M. Grundy, John J.P. Kastelein, Vera Bittner, Jean-Charles Fruchart
Journal: New England Journal of Medicine (2007)

High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol.
Golimumab, a human antibody to tumour necrosis factor given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study
Authors: E C Keystone, M C Genovese, L Klareskog, E C Hsia, S T Hall, P C Miranda, J Pazdur, S-C Bae, W Palmer, J Zrubek, M Wiekowski, S Visvanathan, Z Wu, M U Rahman
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. <h3>Methods:</h3> Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. <h3>Results:</h3> The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p&lt;0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p&lt;0.001) and 0.50 (p&lt;0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively. <h3>Conclusion:</h3> The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.