tbuckley/cabot-search huggingface dataset:
Reflex vascular capacity reduction in the dog.
Authors: C F Rothe
Journal: Circulation Research (1976)

The maximum degree and time course of active reflex venoconstriction in chloralose-anesthetized dogs was studied. The mean circulatory filling pressure (Pmc) was measured by fibrillating the heart and rapidly pumping blood from the aorta to the vena cava until the systemic arterial pressure equaled the central venous pressure. Ventricular fibrillation was continued for 1 minute and was assumed to induce maximal sympathetic discharge to the capacity vessels. Blood was removed to maintain the Pmc constant at the level determined at 8 seconds after the start of fibrillation. It was necessary to remove 13.8 ml/kg by the end of 1 minute. After autonomic nervous system blockade by hexamethonium only 4.8 ml/kg were removed to hold the Pmc constant. Thus, in conclusion, the maximal degree of active venoconstriction induced by circulatory arrest was 9.0 ml/kg during the 1st minute of cardiac fibrillation. A basal capacity vessel tone was present, equivalent to 10 ml/kg under the experimental conditions used.
Lin−Sca-1+CD49fhigh Stem/Progenitors Are Tumor-Initiating Cells in the <i>Pten</i>-Null Prostate Cancer Model
Authors: David J. Mulholland, Li Xin, Ashkan Morim, Devon Lawson, Owen Witte, Hong Wu
Journal: Cancer Research (2009)

Abstract We have shown previously that Pten deletion leads to the expansion of subset of prostate cancer cells positive for CK5 and p63. Although this subpopulation may be involved in tumor initiation or progression, studies to date have not functionally validated this hypothesis. Using in vitro sphere-forming assay and in vivo prostate reconstitution assay, we show here the presence of a tumor-initiating subpopulation in the Pten prostate cancer mouse model. Specifically, we show that the Lin−Sca-1+CD49fhigh (LSC) subpopulation overlaps with CK5+;p63+ cells and is significantly increased during prostate cancer initiation and progression and after castration. Mutant spheres mimic the structural organization of the epithelial compartment in the Pten-null primary tumor. Sorted LSC cells from either Pten-null spheres or primary tumors are able to regenerate prostate epithelial structure with cancerous morphology, closely mimicking that of primary cancers. Therefore, the LSC subpopulation is capable of initiating a cancerous phenotype that recapitulates the pathology seen in the primary lesions of the Pten mutant prostate model. [Cancer Res 2009;69(22):8555–62]
Nrf2 deficiency prevents reductive stress-induced hypertrophic cardiomyopathy
Authors: Sankaranarayanan Kannan, Vasanthi R. Muthusamy, Kevin J. Whitehead, Li Wang, Aldrin V. Gomes, Sheldon E. Litwin, Thomas W. Kensler, E. Dale Abel, John R. Hoidal, Namakkal S. Rajasekaran
Journal: Cardiovascular Research (2013)

Mutant protein aggregation (PA) cardiomyopathy (MPAC) is characterized by reductive stress (RS), PA (of chaperones and cytoskeletal components), and ventricular dysfunction in transgenic mice expressing human mutant CryAB (hmCryAB). Sustained activation of nuclear erythroid-2 like factor-2 (Nrf2) causes RS, which contributes to proteotoxic cardiac disease. The goals of this pre-clinical study were to (i) investigate whether disrupting Nrf2-antioxidant signalling prevents RS and rescues redox homeostasis in hearts expressing the mutant chaperone and (ii) elucidate mechanisms that could delay proteotoxic cardiac disease. Non-transgenic (NTG), transgenic (TG) with MPAC and MPAC-TG:Nrf2-deficient (Nrf2-def) mice were used in this study. The effects of Nrf2 diminution (Nrf2±) on RS mediated MPAC in TG mice were assessed at 6–7 and 10 months of age. The diminution of Nrf2 prevented RS and prolonged the survival of TG mice (∼50 weeks) by an additional 20–25 weeks. The TG:Nrf2-def mice did not exhibit cardiac hypertrophy at even 60 weeks, while the MPAC-TG mice developed pathological hypertrophy and heart failure starting at 24–28 weeks of age. Aggregation of cardiac proteins was significantly reduced in TG:Nrf2-def when compared with TG mice at 7 months. Preventing RS and maintaining redox homeostasis in the TG:Nrf2-def mice ameliorated PA, leading to decreased ubiquitination of proteins. Nrf2 deficiency rescues redox homeostasis, which reduces aggregation of mutant proteins, thereby delaying the proteotoxic pathological cardiac remodelling caused by RS and toxic protein aggregates.
Episodes of Mood Disorders in 2,252 Pregnancies and Postpartum Periods
Authors: Adele C. Viguera, Leonardo Tondo, Alexia E. Koukopoulos, Daniela Reginaldi, Beatrice Lepri, Ross J. Baldessarini
Journal: American Journal of Psychiatry (2011)

Mood disorder in over 2,200 pregnancies of over 1,100 women was examined to determine the risk for an episode. Among these women, 22.7% of those with bipolar disorder experienced an episode during pregnancy and 51.5% during the postpartum period. In comparison, 4.6% of those with unipolar disorder experienced an episode during pregnancy and 29.8% during the postpartum period. First lifetime episodes of mood disorder during the perinatal period occurred for 7.6% of women. Women who already had a mood disorder before their first pregnancy had the highest risk. These high risks are consistent with recommendations for close monitoring and continued treatment during and after pregnancy.
Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. German Humalog-CSII Study Group.
Authors: R Renner, A Pfützner, M Trautmann, O Harzer, K Sauter, R Landgraf
Journal: Diabetes Care (1999)

OBJECTIVE: Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin. Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion (CSII) treatment were assessed in an open randomized crossover trial comparing insulin lispro and regular human insulin, both applied with insulin pumps. RESEARCH DESIGN AND METHODS: A total of 113 type 1 patients (60 male, 53 female, age [mean +/- SD] 37 +/- 12 years, duration of diabetes 19 +/- 9 years) participated in this open, randomized crossover study. Both insulins were applied for 4 months each with the appropriate intervals between the prandial insulin bolus and the meal (human insulin: 30 min; lispro: 0 min). Observation parameters were HbA1c, daily and postprandial blood glucose profiles, adverse events, rate of hypoglycemic and hyperglycemic events, number of catheter obstructions, and treatment satisfaction as assessed with an international validated questionnaire. RESULTS: The patients were well controlled with a mean HBA1c of 7.24 +/- 1.0% at baseline. HbA1c decreased in both treatment periods, but it was better during insulin lispro treatment (insulin lispro: 6.8 +/- 0.9%, regular human insulin: 6.9 +/- 1.0%, Friedman's rank-sum test: P &amp;lt; 0.02). In addition, the 1-h and 2-h postprandial rises in blood glucose were significantly lower (P &amp;lt; 0.001 for each meal) with insulin lispro, resulting in smoother daily glucose profiles as compared with regular human insulin. No significant differences were reported for the rate of hypoglycemia (mean +/- SD [median]: insulin lispro 12.4 +/- 13.9 [8], regular human insulin 11.0 +/- 11.2 [8]), for the rate of catheter obstructions (42 events in each treatment arm), and for the number and type of adverse events. No severe case of ketoacidosis was seen during insulin lispro treatment, whereas one case was reported during therapy with regular human insulin. Treatment satisfaction was better when patients were treated with insulin lispro. CONCLUSIONS: Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment. Its safety profile does not differ from that of regular human insulin.
Effect of tadalafil on anaerobic performance indices in healthy athletes
Authors: L Guidetti, G P Emerenziani, M C Gallotta, F Pigozzi, L Di Luigi, C Baldari
Journal: British Journal of Sports Medicine (2007)

Given the therapeutic and non-therapeutic use of the tadalafil, (phosphodiesterase-5 inhibitor, PDE-5i), we examined its effects on anaerobic performance indices.In total, 12 well-trained subjects reported to the laboratory on two occasions 1 week apart to perform a 30 s Wingate anaerobic power test (WAnT) on a bicycle ergometer. The day before the WAnT, the subjects were double-blinded to receive an oral dose of tadalafil (20 mg) or placebo. Blood lactate value at rest and 1, 3, 6 and 10 minutes of recovery phase, mean power, peak power, time to peak power and fatigue index were assessed for each WAnT.Blood lactate values at the 3-min recovery WAnT increased significantly in the tadalafil condition (mean (SD) 13.9 (1.7) v 12.8 (1.3) mmol/l; p<0.05) and time to peak power decreased significantly (6.3 (1.3) v 5.7 (1.5) s; p = 0.05). No differences were observed in any other parameters between the two conditions.The primary finding of this investigation was that the administration of a single dose of a long-term PDE-5i does not substantially influence anaerobic performance indices. However, results demonstrated both an increase in lactate values at the 3-min point of the recovery phase and a decrease in time to peak power.
Pharmacogenomics: marshalling the human genome to individualise drug therapy
Authors: W E Evans
Journal: Gut (2003)

Pharmacogenomics aims to identify the inherited basis for interindividual differences in drug response, and translate this to molecular diagnostics that can be used to individualise drug therapy. This review uses a number of published examples of inherited differences in drug metabolising enzymes, drug transporters, and drug targets (for example, receptors) to illustrate the potential importance of inheritance in determining the efficacy and toxicity of medications in humans. It seems that this field is at the early stages of developing a powerful set of molecular diagnostics that will have profound utility in optimising drug therapy for individual patients.
Definition of an Enhanced Immune Cell Therapy in Mice That Can Target Stem-Like Lymphoma Cells
Authors: Christopher H. Contag, Rachel Sikorski, Robert S. Negrin, Tobi Schmidt, Alice C. Fan, Pavan Bachireddy, Dean W. Felsher, Steve H. Thorne
Journal: Cancer Research (2010)

Abstract Current treatments of high-grade lymphoma often have curative potential, but unfortunately many patients relapse and develop therapeutic resistance. Thus, there remains a need for novel therapeutics that can target the residual cancer cells whose phenotypes are distinct from the bulk tumor and that are capable of reforming tumors from very few cells. Oncolytic viruses offer an approach to destroy tumors by multiple mechanisms, but they cannot effectively reach residual disease or micrometastases, especially within the lymphatic system. To address these limitations, we have generated immune cells infected with oncolytic viruses as a therapeutic strategy that can combine effective cellular delivery with synergistic tumor killing. In this study, we tested this approach against minimal disease states of lymphomas characterized by the persistence of cancer cells that display stem cell–like properties and resistance to conventional therapies. We found that the immune cells were capable of trafficking to and targeting residual cancer cells. The combination biotherapy used prevented relapse by creating a long-term, disease-free state, with acquired immunity to the tumor functioning as an essential mediator of this effect. Immune components necessary for this acquired immunity were identified. We further demonstrated that the dual biotherapy could be applied before or after conventional therapy. Our approach offers a potentially powerful new way to clear residual cancer cells, showing how restoring immune surveillance is critical for maintenance of a disease-free state. Cancer Res; 70(23); 9837–45. ©2010 AACR.
The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis
Authors: L G M van Baarsen, M J H de Hair, T H Ramwadhdoebe, IJ A J Zijlstra, M Maas, D M Gerlag, P P Tak
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease of unknown aetiology. Recent work has shown that systemic autoimmunity precedes synovial inflammation, and animal models have suggested that changes in the lymph nodes may precede those in the synovial tissue. Therefore, we investigated the cellular composition of the lymph node in the earliest phases of inflammatory arthritis. <h3>Methods</h3> Thirteen individuals positive for immunoglobulin M (IgM) rheumatoid factor and/or anticitrullinated protein antibodies without arthritis were included. Additionally, we studied 14 early arthritis patients (arthritis duration ≤6 months, naïve for disease-modifying antirheumatic drugs), and eight healthy controls. All subjects underwent ultrasound-guided inguinal lymph node biopsy. Different T- and B-lymphocyte subsets were analysed by multicolour flow cytometry. <h3>Results</h3> There was an increase in activated CD69 CD8 T cells and CD19 B cells in early arthritis patients compared with healthy controls. We also observed a trend towards increased CD19 B cells in autoantibody-positive individuals without arthritis compared with healthy controls. <h3>Conclusions</h3> This exploratory study suggests that there is increased immune cell activation within lymph nodes of early arthritis patients as well as in autoantibody-positive individuals at risk of developing RA. This method provides a unique tool to investigate immunological changes in the lymph node compartment in the earliest phases of inflammatory arthritis.
Effects of hemorrhage on renal nerve activity in conscious dogs.
Authors: H Morita, S F Vatner
Journal: Circulation Research (1985)

We studied the effects of slow continuous hemorrhage (0.5 ml/kg per min) on measurements of arterial and left atrial pressures, and renal nerve activity in conscious dogs with all reflexes intact, or after sinoaortic baroreceptor denervation, cardiac denervation, or sinoaortic baroreceptor denervation plus vagal denervation. In intact dogs, mean arterial pressure remained relatively constant at 101 +/- 4 mm Hg until 20 +/- 4 ml/kg of hemorrhage, when renal nerve activity increased by 211 +/- 53%. At 39 +/- 2 ml/kg hemorrhage, mean arterial pressure fell by 48 +/- 3 mm Hg, and renal nerve activity returned to the prehemorrhage control level. Cardiac denervation did not affect the response of mean arterial pressure to hemorrhage, whereas, after sinoaortic baroreceptor denervation and sinoaortic baroreceptor plus vagal denervation, mean arterial pressure remained at its control level only through 8 +/- 1 and 4 +/- 1 ml/kg hemorrhage, respectively. The increases in renal nerve activity during nonhypotensive hemorrhage were significantly attenuated by either sinoaortic baroreceptor or cardiac denervation, and were completely blocked by sinoaortic baroreceptor plus vagal denervation. However, the decline in renal nerve activity with hypotensive hemorrhage was not blocked by either cardiac or sinoaortic baroreceptor denervation, and was enhanced after sinoaortic baroreceptor plus vagal denervation. Our data indicate that nonhypotensive hemorrhage in the conscious dog elicits a striking increase in renal nerve activity, which then returns to control levels during hypotensive hemorrhage. Both sinoaortic and cardiopulmonary baroreceptors are involved in mediating the increase in renal nerve activity, whereas the decline in renal nerve activity is not due to either of these baroreflexes.
Transient collateral augmentation during coronary arterial spasm associated with ST-segment depression.
Authors: M Tada, M Yamagishi, K Kodama, T Kuzuya, S Nanto, M Inoue, H Abe
Journal: Circulation (1983)

To examine the possible existence of collateral circulation during coronary artery spasm, we attempted to visualize the transient appearance of collateral vessels that could serve to salvage otherwise jeopardized ischemic areas. In three patients with vasospastic angina, total spastic obstruction of a major coronary artery was associated with transient collateral augmentation, which was supplied by the nonspastic artery during anginal period associated with ST-segment depression. These collateral vessels disappeared when the angina and ST changes resolved after nitroglycerin administration. These findings suggest that the collateral blood supply could transiently occur through preexisting vessels to perfuse the ischemic area during coronary artery spasm and that such collateral flow could have a role in preventing transmural myocardial ischemia, resulting in a lesser degree of ischemia associated with ST-segment depression.
Prenatal methylmercury exposure from ocean fish consumption in the Seychelles child development study
Authors: Gary J Myers, Philip W Davidson, Christopher Cox, Conrad F Shamlaye, Donna Palumbo, Elsa Cernichiari, Jean Sloane-Reeves, Gregory E Wilding, James Kost, Li-Shan Huang, Thomas W Clarkson
Journal: The Lancet (2003)
Altitude, Gun Ownership, Rural Areas, and Suicide
Authors: Namkug Kim, Jennie B. Mickelson, Barry E. Brenner, Charlotte A. Haws, Deborah A. Yurgelun-Todd, Perry F. Renshaw
Journal: American Journal of Psychiatry (2010)

Objective: The authors recently observed a correlation between state altitude and suicide rate in the United States, which could be explained by higher rates of gun ownership and lower population density in the intermountain West. The present study evaluated the relationship between mean county and state altitude in the United States and total age-adjusted suicide rates, firearm-related suicide rates, and non-firearm-related suicide rates. The authors hypothesized that altitude would be significantly associated with suicide rate. Method: Elevation data were calculated with an approximate spatial resolution of 0.5 km, using zonal statistics on data sets compiled from the National Geospatial-Intelligence Agency and the National Aeronautics and Space Administration. Suicide and population density data were obtained through the Centers for Disease Control and Prevention (CDC) WONDER database. Gun ownership data were obtained through the CDC's Behavioral Risk Factor Surveillance System. Results: A significant positive correlation was observed between age-adjusted suicide rate and county elevation (r=0.51). Firearm (r=0.41) and non-firearm suicide rates (r=0.32) were also positively correlated with mean county elevation. Conclusions: When altitude, gun ownership, and population density are considered as predictor variables for suicide rates on a state basis, altitude appears to be a significant independent risk factor. This association may be related to the effects of metabolic stress associated with mild hypoxia in individuals with mood disorders.
Antiribosomal P protein IgG autoantibodies are highly specific for SLE and might be associated with disease activity
Authors: D. Fernandes, M. Santos, J. Fonseca
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Systemic lupus erythematosus (SLE) is characterised by the production of autoantibodies directed against a variety of nuclear and cytoplasmic antigens. One of these antigens is ribosomal P protein (Rib-P), a pentamer consisting of three different phosphoproteins. The aim of this work was to assess the prevalence and clinical associations of anti-Rib-P antibodies in a cohort of Portuguese SLE patients. <h3>Patients and methods</h3> Anti-Rib-P autoantibodies were quantified in sera from 127 SLE patients, 100 healthy controls and 256 various control diseases including rheumatoid arthritis (n=100), JIA (n=34), AS (n=100) and PsA (n=22) using the EliA Rib-P (Phadia, Sweden), a fluoroenzymeimmunoassay that quantifies Rib-P specific IgG antibodies. <h3>Results</h3> The mean value of anti-Rib-P was significantly higher in SLE patients than in healthy (p&lt;0.001) or disease control population (p=0.002). Setting the cut-off for positivity at 4.45 U/ml as determined by Receiver Operating Characteristic (ROC) curve analysis, 18 SLE patients (14.2%) but no healthy controls were positive for anti-Rib-P autoantibodies (Rib-P-(+)) (p&lt;0.001); in the disease control group only two rheumatoid arthritis patients were Rib-P-(+) (p&lt;0.001). The area under the curve was 0.800 for discrimination between SLE and healthy controls (sensitivity=14.2%; specificity=100%) and 0.595 for control diseases (sensitivity=14.2%; specificity=99.2%). SLE patients Rib-P-(+) had a higher SLEDAI (p=0.005), but no association with psychosis or nephritis was found. Also there was no relation with age, age at diagnosis, gender or ethnicity. The authors also compared anti-Rib-P autoantibodies with the production of other autoantibodies (such as anti-dsDNA, anti-Sm or APL) and found no statistically significant associations. <h3>Conclusion</h3> Considering the high specificity of this test, the authors believe that anti-Rib-P autoantibody quantification through this method might be useful in SLE diagnosis. Its value as an indicator of active disease needs to be prospectively validated.
Characterization of occult hepatitis B virus strains in south african blood donors
Authors: Jean‐Pierre Allain, Dalila Belkhiri, Marion Vermeulen, Robert Crookes, Russell Cable, Azin Amiri, Ravi Reddy, Arthur Bird, Daniel Candotti
Journal: Hepatology (2009)

Since October 2005, all blood units collected in South Africa were screened individually for human immunodeficiency virus (HIV)-1, hepatitis B and C virus (HBV, HCV) genomes uncovering preseroconversion window period (WP) infections for each virus and occult HBV infections (OBIs) defined as persistent HBV DNA without detectable hepatitis B surface antigen (HBsAg). Samples identified as HBsAg-negative/DNA-positive were confirmed by combining real-time quantitative polymerase chain reaction, nested amplification, anti-HBc and anti-HBs. Amplified basic core promoter/precore, pre-S/S, and whole genome were sequenced, analyzed, and compared to 73 HBsAg+ strains. Genotype was determined by phylogenetic analysis. From 109 samples examined, 54 were classified as OBI, 14 as WP, 20 as false-positive, five as other classification, and 16 as undetermined due to lack of serological or follow-up data. OBI donors were predominantly males (67%), median age 31 years, black (54%), with normal alanine aminotransferase levels. Viral load ranged between unquantifiable and 518 IU/mL (median 5 IU/mL). Genotype A1 was more frequent (23 strains) than genotype D (seven strains). Genotype A1 strains were little mutated. In the major hydrophilic region, 56.5% strains were wild type or with few amino acid substitutions. Most important, all 13 full genome sequences presented 1 to 7 mutations known to or assumed to negatively impact viral replication. In particular, 6/13 sequences had a stop codon in the HBx gene translated into deletion of 117 or 19-25 C-terminus amino acids not found in 15 HBeAg+ HBsAg+ strains. One WP sequence with an HBx stop codon suggested infectivity. Conclusion: Genotype A1 OBIs are different from genotype A2 and D OBIs in that there is little evidence of immune pressure as a major factor involved in OBI genesis. Limited replication appears mostly related to genetic viral defects. (HEPATOLOGY 2009.)