tbuckley/cabot-search huggingface dataset:
Characterization of high and low pressure baroreceptor influences on renal nerve activity in the primate Macaca fascicularis.
Authors: S F Echtenkamp, I H Zucker, J P Gilmore
Journal: Circulation Research (1980)

We characterized the influence of high pressure and low pressure intravascular receptors on renal nerve activity in the pentobarbital sodium-anesthetized nonhuman primate Macaca fascicularis. Epinephrine-induced increases in arterial pressure were used to stimulate high pressure receptors, and intravascular volume expansion was used to stimulate both high and low pressure receptors. In addition, the intravascular mechanoreceptors were stimulated directly by intravenous veratrine administration. All interventions produced large decreases in renal nerve activity in the intact state. Denervation of the carotid sinus or bilateral cervical vagal section dimished, whereas sinoaortic denervation with vagotomy completely abolished all responses of renal activity to these interventions. We conclude that the nonhuman primate possesses very sensitive renal nerve sympathetic reflexes that are modulated by intravascular mechanoreceptors whose afferents traverse the carotid sinus nerves and the vago-aortic trunks. The carotid sinus nerves and the vago-aortic trunks appear to be equally effective in inhibiting renal nerve activity in response to increases in arterial pressure. In addition, there are no afferent pathways mediating intravascular mechanoreceptor modulation of renal nerve activity outside the carotid sinus nerves and the vago-aortic trunks.
Exchangeable Potassium Study in Patients Undergoing Chronic Haemodialysis
Authors: Y. K. Seedat
Journal: BMJ (1969)

Seven patients with chronic renal failure treated with haemodialysis for 4 to 24 months were found to have low exchangeable potassium levels. Before dialysis the plasma potassium was normal or somewhat raised (possibly owing to acidosis), though the exchangeable potassium was low. Acidosis was corrected during dialysis; plasma potassium levels fell, but clinical and electrocardiographic changes of hypokalaemia were absent. The level of 1 mEq/litre in the dialysate fluid may be too low for use in prolonged haemodialysis.
Tumor location does not influence the survival effects of radiotherapy in node-negative breast cancer.
Authors: M Royce, C Bouchardy, E Rapiti, G Vlastos, G Cserni, V Vinh-Hung, J Lamote, G Storme, NP Nguyen, PT Truong
Journal: Cancer Research (2009)

Abstract Abstract #4134 Background&amp;#x2028; Medial (inner quadrants) tumor location has been shown to adversely influence survival in breast cancer. We investigated whether tumor location should alter the choice of local-regional treatments (surgery, with or without radiation therapy - RT), in women with node-negative breast cancer.&amp;#x2028; Materials and methods&amp;#x2028; Data were abstracted from the Surveillance, Epidemiology, and End Results (SEER) 2006's database for 58,709 women aged 25-95 years, diagnosed between 1988-1997 with non-metastatic T1-2 node-negative breast cancer, who underwent breast conserving surgery (BCS) and axillary dissection. We used Cox proportional hazards to examine the effect of tumor location (medial versus other) on overall mortality after accounting for other prognostic factors (covariates listed in footnote table 1) and interactions identified by the Akaike Information Criteria.&amp;#x2028; Results&amp;#x2028; There were no notable differences in patients' characteristics according to tumor location. Among them, 25,232 had BCS, 33,477 had mastectomy. However the distribution according to the use of adjuvant RT showed marked heterogeneity. RT was used in 88% of BCS and in 3% of mastectomy patients. In the multivariate analysis that adjusted against the imbalances, medial location was associated with an increased mortality, hazard ratio (HR) 1.08 (95% confidence interval 1.04-1.13). Mastectomy had no significant impact on survival, HR=0.99 (0.92-1.07). RT was associated with a significant mortality reduction, HR=0.81 (0.75-0.88). There was no interaction between tumor location and surgery, or between tumor location and RT, while the interaction between surgery and RT was significant, HR=1.31 (1.14-1.51). The corresponding factorial summary showed no subgroup effect of tumor location: RT after BCS was associated with the same mortality reduction of 19% regardless of tumor location, and RT after mastectomy was associated with the same relative increase of 7% regardless of tumor location (Table 1).&amp;#x2028; Conclusion&amp;#x2028; We confirm the poorer prognosis associated with tumor medial location. However there was no subgroup effect. The survival outcomes of local-regional treatments were not affected by tumor location, arguing that tumor location is not a sufficient indication to modify local-regional treatments in node-negative patients. Local-regional treatment should be based on tumor characteristics and not tumor location.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4134.
Interaction between microvascular alpha 1- and alpha 2-adrenoceptors and endothelium-derived relaxing factor.
Authors: M Ohyanagi, K Nishigaki, J E Faber
Journal: Circulation Research (1992)

Intravital microscopy was used to study the effect of endothelium-derived relaxing factor (EDRF) on microvascular adrenoceptor sensitivity in rat cremaster skeletal muscle. NG-Monomethyl L-arginine (L-NMMA, 1-300 microM), an inhibitor of EDRF formation, produced concentration-dependent constriction of arterioles and venules. When an intermediate amount of alpha 1- versus alpha 2-adrenoceptor tone was first produced with bath-added norepinephrine (NE) in the presence of rauwolscine or prazosin, L-NMMA caused constriction with greater potency and efficacy during alpha 2 than during alpha 1 tone. During localized alpha 1 or alpha 2 constriction along an arteriole by perivascular micropipette suffusion of NE in the presence of rauwolscine or prazosin, again, bath-added L-NMMA produced constriction with greater potency during alpha 2 than during alpha 1 constriction. Like L-NMMA, disruption of EDRF release by microembolization caused baseline arteriole constriction and selectively increased alpha 2 sensitivity 75-fold. Although these findings support the hypothesis that endothelial cells possess alpha 2-adrenoceptors that promote EDRF release, a greater susceptibility of alpha 2 than alpha 1 constriction to EDRF inhibition could also account for the results. In support of this latter possibility, alpha 2 constriction was approximately 50-fold more susceptible than alpha 1 constriction to inhibition by the EDRF-like nitrodilator nitroprusside. The similarity in magnitude of this difference in sensitivity with the difference obtained in the embolization experiments does not support the hypothesis that microvascular endothelial cells in skeletal muscle possess EDRF-promoting alpha 2-adrenoceptors. However, these data do suggest that endogenous EDRF release modulates basal arteriole and venule tone and that alpha 2-adrenoceptor constriction is more sensitive than alpha 1 constriction to inhibition by EDRF.
Phase I Pharmacokinetic and Pharmacodynamic Study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, an Inhibitor of Heat-Shock Protein 90, in Patients With Advanced Solid Tumors
Authors: Ramesh K. Ramanathan, Merrill J. Egorin, Charles Erlichman, Scot C. Remick, Suresh S. Ramalingam, Cynthia Naret, Julianne L. Holleran, Cynthia J. TenEyck, S. Percy Ivy, Chandra P. Belani
Journal: Journal of Clinical Oncology (2010)

To define the maximum tolerated dose, toxicities, pharmacokinetics, and pharmacodynamics of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17DMAG).17DMAG was given intravenously over 1 hour daily for 5 days (schedule A) or daily for 3 days (schedule B) every 3 weeks. Plasma 17DMAG concentrations were measured by liquid chromatography/mass spectrometry. Heat-shock proteins (HSPs) and client proteins were evaluated at baseline and after treatment on day 1 in peripheral blood mononuclear cells (PBMCs) and in pre- and post-treatment (24 hours) biopsies done during cycle 1 at the recommended phase II dose (n = 7).Fifty-six patients were entered: 26 on schedule A; 30 on schedule B. The recommended phase II doses for schedules A and B were 16 mg/m(2) and 25 mg/m(2), respectively. Grade 3/4 toxicities included liver function test elevation (14%), pneumonitis (9%), diarrhea (4%), nausea (4%), fatigue (4%) and thrombocytopenia (4%). There were no objective responses. Four patients had stable disease. 17DMAG half-life was 24 +/- 15 hours. 17DMAG area under the curve (range, 0.7 to 14.7 mg/mL x h) increased linearly with dose. The median HSP90, HSP70, and integrin-linked kinase levels were 87.5% (n = 14), 124% (n = 20), and 99.5% (n = 20) of baseline. Changes in HSPs and client proteins in tumor biopsies were not consistent between baseline and 24 hours nor did they change in the same direction as those in PBMCs collected at the time of biopsy.The recommended phase II doses of 17DMAG (16 mg/m(2) x 5 days or 25 mg/m(2) x 3 days, every 3 weeks) are well tolerated and suitable for further evaluation.
Multiple Sclerosis and Human Interferon Alfa
Authors: J. Terrence Coyle
Journal: JAMA (1989)

To the Editor.—  Larrey et al 1 describe  case of multiple sclerosis supposedly aggravated by the administration of recombinant human interferon alfa. Three hours after receiving interferon, the patient developed  high-grade  followed in 1 hour by marked weakness; within 4 hours the patient became quadriplegic. He improved spontaneously and in 1 month had no residual findings. The authors' interpretation was that  observation suggests that interferon alfa can induce exacerbations of multiple sclerosis.  A more likely explanation for the transitory aggravation of symptoms was the induction of a high-grade fever rather than  reaction to interferon. Hyperthermia in patients with multiple sclerosis can aggravate or even make manifest new symptoms of multiple sclerosis (Uhthoff's phenomenon). 2 The authors could check this by inducing hyperthermia. There is some risk, as permanent neurological loss has been reported; however, merely raising the body temperature slightly by  hot shower or
Effect of inhaled glucocorticoids on IL-1 beta and IL-1 receptor antagonist (IL-1 ra) expression in asthmatic bronchial epithelium
Authors: A. R. Sousa, C. J. Trigg, S. J. Lane, R. Hawksworth, J. A. Nakhosteen, R. N. Poston, T. H. Lee
Journal: Thorax (1997)

BACKGROUND: Accumulating evidence suggests that the cytokine network is central to the immunopathology of bronchial asthma and the existence of naturally occurring cytokine antagonists has added to this complexity. Upregulation of both interleukin 1 beta (IL-1 beta) and its naturally occurring receptor antagonist, interleukin 1 receptor antagonist (IL-1ra), has previously been observed on asthmatic bronchial epithelium compared with normal airways. METHODS: The effect of inhaled beclomethasone dipropionate (BDP) on asthmatic bronchial epithelial expression of IL-1 beta and IL-1ra was studied. Frozen bronchial biopsy specimens from nine asthmatic subjects receiving 1000 micrograms BDP daily for eight weeks and from six asthmatic subjects receiving matching placebo were stained with anti-IL-1 beta and anti-IL-1ra antibodies. Hue-saturation-intensity (HSI) colour image analysis was used to quantify the brown immunoperoxidase reaction colour present on the bronchial epithelium. RESULTS: There was a significant twofold decrease in the epithelial expression of IL-1 beta after treatment with BDP but no significant change was seen in IL-1ra (P = 0.175). CONCLUSION: The selective inhibition of IL-1 beta, without effect on IL-1ra, provides a novel mechanism for the anti-inflammatory action of glucocorticosteroids.
A NEW FINSEN LAMP FOR LOCAL TREATMENT OF THE SKIN*
Authors: SVEND LOMHOLT
Journal: British Journal of Dermatology (1928)

Journal Article A NEW FINSEN LAMP FOR LOCAL TREATMENT OF THE SKIN Get access SVEND LOMHOLT, O.B.E., M.D. SVEND LOMHOLT, O.B.E., M.D. Finsen Institute, Copenhagen Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 40, Issue 12, 1 December 1928, Pages 494–496, https://doi.org/10.1111/j.1365-2133.1928.tb13639.x Published: 01 December 1928
Prevention of Postpartum Depression: A Pilot Randomized Clinical Trial
Authors: Katherine L. Wisner, James M. Perel, Kathleen S. Peindl, Barbara H. Hanusa, Catherine M. Piontek, Robert L. Findling
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors attempted to reduce the rate of postpartum depression in high-risk women and to increase the time to recurrence. METHOD: Nondepressed pregnant women with at least one past episode of postpartum major depression were recruited into a randomized clinical trial. Mothers were assigned randomly to a 17-week trial of sertraline or placebo immediately after birth and assessed for 20 sequential weeks with the Hamilton Rating Scale for Depression. RESULTS: Of 14 subjects who took sertraline, one (7%) suffered a recurrence. Of eight subjects who were assigned to placebo, four (50%) suffered recurrences. This difference was significant. The time to recurrence was significantly longer in the sertraline-treated women than in the placebo-treated women. CONCLUSIONS: Sertraline conferred preventive efficacy for postpartum-onset major depression beyond that of placebo.
Intracellular action potential changes induced in both ventricles of the rat by an acute right ventricular pressure overload
Authors: J BOLAND, J TROQUET
Journal: Cardiovascular Research (1980)

Eleven open chest, artificially ventilated rats were used to observe and compare the intracellular potential changes induced in the right and left ventricles by an acute right ventricular overload. Graded right ventricular hypertension was produced by external constriction of the main pulmonary artery. Transmembrane potentials were obtained using floating glass microelectrodes filled with 3 mol·litre−1 KCl and connected to a cathode follower through a silverchloride-silver junction. Following right ventricular overload, the level of the resting potential was depolarised by 20% on the right ventricle and by 4% on the left (P <0.001). The repolarisation was not significantly affected. A significant correlation (P <0.01) was observed between the increase of right ventricular pressure and the depolarisation of resting right ventricular potential. The right ventricular distension which occurs in our experimental model thus induces a diastolic depolarisation of right ventricular muscle cells which cannot be neglected in the interpretation of the peripheral ECG changes.
Measurement of lung volumes by plethysmography
Authors: AL Coates, R Peslin, D Rodenstein, J Stocks
Journal: European Respiratory Journal (1997)

There are various ways of measuring absolute lung volume. These range from measurements derived from chest radiographs to the more common laboratory measurements employing either gas dilution or plethysmography. The principal difference between the latter two methods is that gas dilution techniques measure gas that is in free communication with the airway opening, whilst plethysmography measures all intrathoracic gas. Once the absolute lung volume is known, the other lung volumes can be measured from the change in volume
Rate Variation Among Nuclear Genes and the Age of Polyploidy in Gossypium
Authors: David S. Senchina, Ines Alvarez, Richard Clark Cronn, Bao Liu, Junkang Rong, Richard D. Noyes, Andrew H. Paterson, Rod A. Wing, Thea A. Wilkins, Jonathan F. Wendel
Journal: Molecular Biology and Evolution (2003)

Molecular evolutionary rate variation in Gossypium (cotton) was characterized using sequence data for 48 nuclear genes from both genomes of allotetraploid cotton, models of its diploid progenitors, and an outgroup. Substitution rates varied widely among the 48 genes, with silent and replacement substitution levels varying from 0.018 to 0.162 and from 0.000 to 0.073, respectively, in comparisons between orthologous Gossypium and outgroup sequences. However, about 90% of the genes had silent substitution rates spanning a more narrow threefold range. Because there was no evidence of rate heterogeneity among lineages for any gene and because rates were highly correlated in independent tests, evolutionary rate is inferred to be a property of each gene or its genetic milieu rather than the clade to which it belongs. Evidence from approximately 200,000 nucleotides (40,000 per genome) suggests that polyploidy in Gossypium led to a modest enhancement in rates of nucleotide substitution. Phylogenetic analysis for each gene yielded the topology expected from organismal history, indicating an absence of gene conversion or recombination among homoeologs subsequent to allopolyploid formation. Using the mean synonymous substitution rate calculated across the 48 genes, allopolyploid cotton is estimated to have formed circa 1.5 million years ago (MYA), after divergence of the diploid progenitors about 6.7 MYA.
Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy
Authors: E. Arnaudo, S. Shanske, S. DiMauro, E.A. Schon, C.T. Moraes, E.A. Schon, M. Dalakas
Journal: The Lancet (1991)

Long-term zidovudine therapy in patients with human immunodeficiency virus (HIV) infection can cause a destructive mitochondrial myopathy with histological features of ragged-red fibres (RRF) and proliferation of abnormal mitochondria. In 9 zidovudine-treated patients with this myopathy we found severely reduced amounts (up to 78% reduction vs normal adult controls) of mitochondrial DNA (mtDNA) in muscle biopsy specimens by means of Southern blotting. In 2 HIV-positive patients who had not received zidovudine, muscle mtDNA content did not differ from that in the 4 controls. Depletion of mtD NA seems to be reversible, since 1 patient showed a substantial reduction in RRF and a concomitant pronounced increase in muscle mtDNA content after zidovudine therapy was discontinued. Depletion of muscle mtDNA is probably due to zidovudine-induced inhibition of mtDNA replication by DNA polymerase gamma and is not a secondary effect of HIV infection.
506 UNDETECTABLE HCV-RNA IN TELAPREVIR-TREATED PATIENTS: LOW CONCORDANCE BETWEEN TWO HIGHLY SENSITIVE REAL-TIME PCR ASSAYS
Authors: J. Vermehren, A. Aghemo, K.-H. Peiffer, S. Susser, R. D'Ambrosio, D. Perner, L. Gerber, R. Soffredini, O. Weiland, S. Zeuzem, M. Colombo, C. Sarrazin
Journal: Journal of Hepatology (2013)
Prenatal dexamethasone exposure induces changes in nonhuman primate offspring cardiometabolic and hypothalamic-pituitary-adrenal axis function
Authors: Annick de Vries, Megan C. Holmes, Areke Heijnis, Jürgen V. Seier, Joritha Heerden, Johan Louw, Sonia Wolfe-Coote, Michael J. Meaney, Naomi S. Levitt, Jonathan R. Seckl
Journal: Journal of Clinical Investigation (2007)

Prenatal stress or glucocorticoid administration has persisting "programming" effects on offspring in rodents and other model species. Multiple doses of glucocorticoids are in widespread use in obstetric practice. To examine the clinical relevance of glucocorticoid programming, we gave 50, 120, or 200 microg/kg/d of dexamethasone (dex50, dex120, or dex200) orally from mid-term to a singleton-bearing nonhuman primate, Chlorocebus aethiops (African vervet). Dexamethasone dose-dependently reduced maternal cortisol levels without effecting maternal blood pressure, glucose, electrolytes, or weight gain. Birth weight was unaffected by any dexamethasone dose, although postnatal growth was attenuated after dex120 and dex200. At 8 months of age, dex120 and dex200 offspring showed impaired glucose tolerance and hyperinsulinemia, with reduced (approximately 25%) pancreatic beta cell number at 12 months. Dex120 and dex200 offspring had increased systolic and diastolic blood pressures at 12 months. Mild stress produced an exaggerated cortisol response in dex200 offspring, implying hypothalamic-pituitary-adrenal axis programming. The data are compatible with the extrapolation of the glucocorticoid programming hypothesis to primates and indicate that repeated glucocorticoid therapy and perhaps chronic stress in humans may have long-term effects.
Transcatheter Aortic-Valve Replacement with a Self-Expanding Prosthesis
Authors: David H. Adams, Jeffrey J. Popma, Michael J. Reardon, Steven J. Yakubov, Joseph S. Coselli, G. Michael Deeb, Thomas G. Gleason, Maurice Buchbinder, James Hermiller, Neal S. Kleiman, Stan Chetcuti, John Heiser, William Merhi, George Zorn, Peter Tadros, Newell Robinson, George Petrossian, G. Chad Hughes, J. Kevin Harrison, John Conte, Brijeshwar Maini, Mubashir Mumtaz, Sharla Chenoweth, Jae K. Oh
Journal: New England Journal of Medicine (2014)

We compared transcatheter aortic-valve replacement (TAVR), using a self-expanding transcatheter aortic-valve bioprosthesis, with surgical aortic-valve replacement in patients with severe aortic stenosis and an increased risk of death during surgery.We recruited patients with severe aortic stenosis who were at increased surgical risk as determined by the heart team at each study center. Risk assessment included the Society of Thoracic Surgeons Predictor Risk of Mortality estimate and consideration of other key risk factors. Eligible patients were randomly assigned in a 1:1 ratio to TAVR with the self-expanding transcatheter valve (TAVR group) or to surgical aortic-valve replacement (surgical group). The primary end point was the rate of death from any cause at 1 year, evaluated with the use of both noninferiority and superiority testing.A total of 795 patients underwent randomization at 45 centers in the United States. In the as-treated analysis, the rate of death from any cause at 1 year was significantly lower in the TAVR group than in the surgical group (14.2% vs. 19.1%), with an absolute reduction in risk of 4.9 percentage points (upper boundary of the 95% confidence interval, -0.4; P<0.001 for noninferiority; P = 0.04 for superiority). The results were similar in the intention-to-treat analysis. In a hierarchical testing procedure, TAVR was noninferior with respect to echocardiographic indexes of valve stenosis, functional status, and quality of life. Exploratory analyses suggested a reduction in the rate of major adverse cardiovascular and cerebrovascular events and no increase in the risk of stroke.In patients with severe aortic stenosis who are at increased surgical risk, TAVR with a self-expanding transcatheter aortic-valve bioprosthesis was associated with a significantly higher rate of survival at 1 year than surgical aortic-valve replacement. (Funded by Medtronic; U.S. CoreValve High Risk Study ClinicalTrials.gov number, NCT01240902.).
Gene therapy, regulatory mechanisms, and protein function in vision
Authors: James F. McGinnis
Journal: Behavioral and Brain Sciences (1995)

Abstract Hereditary retinal degeneration due to mutations in visual genes may be amenable to therapeutic interventions that modulate, either positively or negatively, the amount of protein product. Some of the proteins involved in phototransduction are rapidly moved by a lightdependent mechanism between the inner segment and the outer segment in rod photoreceptor cells, and this phenomenon is important in phototransduction.