tbuckley/cabot-search huggingface dataset:
Effects of acetylcholine on action potential characteristics of atrial and ventricular myocardium after bilateral cervical vagotomy in the cat.
Authors: R J Kovacs, J C Bailey
Journal: Circulation Research (1985)

Acetylcholine, the parasympathetic neurotransmitter, shortens the action potential duration of cat atrial muscle cells, but not ventricular muscle cells. In mammalian species, atrial tissue receives a richer cholinergic nerve supply than ventricular tissue. To determine whether chronic withdrawal of cholinergic tone might influence the subsequent response of these tissues to cholinergic stimulation, we examined the effect of acetylcholine on the action potentials of atrial and ventricular myocytes from cats with intact vagi and cats after chronic bilateral cervical vagotomy. Following bilateral cervical vagotomy, physostigmine (10(-6) M) failed to alter atrial tension development or action potential duration. Acetylcholine produced shortening of the action potential duration in atrial muscle from cats with intact vagi and in cats following bilateral cervical vagotomy. However, the degree of shortening produced by acetylcholine after bilateral cervical vagotomy was significantly greater (P less than 0.001). In ventricular muscle from cats with intact vagi, acetylcholine did not alter action potential duration. In ventricular muscle from cats after bilateral cervical vagotomy, acetylcholine shortened the action potential duration. Maximal effect was seen at a concentration of 10(-5) M where acetylcholine shortened action potential duration at 90% repolarization from a control value of 179 +/- 4 to 150 +/- 7 msec. Atropine (10(-6) M) reversed the effects of acetylcholine. Addition of propranolol (10(-6) M) to the superfusate or pretreatment of the animals with reserpine (2 mg/kg, ip) 24 hours before sacrifice failed to alter the response of ventricular muscle cells to acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)
Titin isoform expression in normal and hypertensive myocardium
Authors: C Warren
Journal: Cardiovascular Research (2003)

Titin isoform expression patterns were examined to explain previously observed genetic differences in rat cardiac passive tension.Rat ventricles from male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats (normotensive) were used to analyze the titin isoform patterns. The hypertensive status was verified by blood pressure measurements and heart weight to body weight ratios. Gel electrophoresis and scanning densitometry were performed to determine ratios of myosin heavy chain and titin isoforms expressed. In situ hybridization using a cRNA probe specific for N2BA titin and a positive control in the N2B unique region was used to demonstrate tissue location of the titin message.Regression analysis of titin isoform ratios, myosin heavy chain isoform ratios, and heart weight to body weight ratios all suggest a smaller proportion of N2BA titin (longer isoform) was expressed in rat left ventricles with increased hypertrophy. In situ hybridization showed that the N2BA and N2B isoforms were co-expressed within most of the cardiomyocytes. Agarose gel electrophoresis demonstrated two different N2BA titin isoforms in all rat ventricles.Expression of less N2BA and more N2B titin in response to pressure overload will result in higher passive tension upon stretch at a given sarcomere length and thus affect cardiac performance.
The role of the 5-HT3 antagonists ondansetron and dolasetron in the control of delayed onset nausea and vomiting in patients receiving moderately emetogenic chemotherapy
Authors: J.L. Pater, W.S. Lofters, B. Zee, E. Dempsey, D. Walde, J.-P. Moquin, K. Wilson, P. Hoskins, R.M. Guevin, S. Verma, R. Navari, J.E. Krook, J. Hainsworth, M. Palmer, C. Chin
Journal: Annals of Oncology (1997)
Results of a phase I trial of BAY 43–9006 in combination with doxorubicin in patients with refractory solid tumors
Authors: H. Richly, P. Kupsch, K. Passarge, M. Grubert, R. A. Hilger, C. G. Haase, B. Schwartz, M. E. Scheulen, S. Seeber, D. Strumberg
Journal: Journal of Clinical Oncology (2004)

3049 Background:BAY 43–9006 (BAY) is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-β. Previous single-agent phase I studies show BAY is well tolerated, with manageable and reversible side effects, most commonly hand-foot skin (HFS) reaction, rash, fatigue, and diarrhea. This phase I study was initiated to determine the safety and pharmacokinetics (PK) of BAY in combination with doxorubicin. Methods:Patients (pts) received a fixed dose of doxorubicin (60 mg/m2 q x 3weeks) starting on day 1 of cycle 1 (C1). BAY was given on days 4–21 in C1 and continuously thereafter. BAY doses were 100 mg bid (cohort 1) escalating to 200 mg bid (cohort 2) and 400 mg bid (cohorts 3 and 4). Results:34 pts (M:F, 21:13; median age 60 yrs range 33–73) were treated. Common tumor types were CRC (15%), pancreatic cancer (15%) and HCC (12%). Dose-limiting leuko/neutropenia was seen in cohort 1 (1/6 pts) and cohort 3 (6/22 pts); all were related to doxorubicin therapy. Dose-limiting grade 3 skin toxicity (HFS reaction) occurred in 4/22 pts in cohort 3, which was related to BAY therapy. Non-DLTs were doxorubicin-related leuko/neutropenia, occurring 3 times in cohort 1, 4 times in cohort 3, and 2 times in cohort 4, and BAY-related HFS reactions in 5 pts from cohort 3. Steady-state BAY PK was not significantly influenced by concomitant doxorubicin medication when C1 and C2 were compared. Multiple BAY dosing had no consistent effect on the PK of doxorubicin or its metabolite doxorubicinol. Seventeen (53%) pts had a best response according to RECIST of PR (1 pt with mesothelioma) or SD (16 pts); 11 of these pts were from the 400 mg bid cohort. Conclusions:The combination of BAY and doxorubicin appears to be well tolerated and an extension in pts with HCC is ongoing. Most frequent AEs were related to doxorubicin. Most BAY-related AEs were mild (grade 1/2). No clinically relevant PK interaction between BAY and doxorubicin was observed. The recommended dose of BAY for phase II studies in combination with doxorubicin is 400 mg bid BAY. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer AG, Wuppertal, Germany, Bayer Corp. Bayer AG, Wuppertal, Germany
The Growth of Palliative Care in the United States
Authors: Mark T. Hughes, Thomas J. Smith
Journal: Annual Review of Public Health (2014)

Palliative care has been one of the most rapidly growing fields of health care in the United States in the past decade. The benefits of palliative care have now been shown in multiple clinical trials, with increased patient and provider satisfaction, equal or better symptom control, more discernment of and honoring choices about place of death, fewer and less intensive hospital admissions in the last month of life, less anxiety and depression, less caregiver distress, and cost savings. The cost savings come from cost avoidance, or movement of a patient from a high cost setting to a lower cost setting. Barriers to expanded use include physician resistance, unrealistic expectations of patients and families, and lack of workforce. The future of palliative care includes more penetration into other fields such as nephrology, neurology, and surgery; further discernment of the most effective and cost-effective models; and establishment of more outpatient services.
Large IncHI2-plasmids encode extended-spectrum β-lactamases (ESBLs) in Enterobacter spp. bloodstream isolates, and support ESBL-transfer to Escherichia coli
Authors: E. Nilsen, B.C. Haldorsen, A. Sundsfjord, G.S. Simonsen, A. Ingebretsen, U. Naseer, Ø. Samuelsen
Journal: Clinical Microbiology and Infection (2013)
Surface proteins from Helicobacter pylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa.
Authors: U E Mai, G I Perez-Perez, J B Allen, S M Wahl, M J Blaser, P D Smith
Journal: The Journal of Experimental Medicine (1992)

The mechanism by which Helicobacter pylori, a noninvasive bacterium, initiates chronic antral gastritis in humans is unknown. We now show that H. pylori releases products with chemotactic activity for monocytes and neutrophils. This chemotactic activity was inhibited by antisera to either H. pylori whole bacteria or H. pylori-derived urease. Moreover, surface proteins extracted from H. pylori and purified H. pylori urease (a major component of the surface proteins) exhibited dose-dependent, antibody-inhibitable chemotactic activity. In addition, a synthetic 20-amino acid peptide from the NH2-terminal portion of the 61-kD subunit, but not the 30-kD subunit, of urease exhibited chemotactic activity for monocytes and neutrophils, localizing the chemotactic activity, at least in part, to the NH2 terminus of the 61-kD subunit of urease. The ability of leukocytes to chemotax to H. pylori surface proteins despite formyl-methionyl-leucyl-phenylalanine (FMLP) receptor saturation, selective inhibition of FMLP-mediated chemotaxis, or preincubation of the surface proteins with antiserum to FMLP indicated that the chemotaxis was not FMLP mediated. Finally, we identified H. pylori surface proteins and urease in the lamina propria of gastric antra from patients with H. pylori-associated gastritis but not from uninfected subjects. These findings suggest that H. pylori gastritis is initiated by mucosal absorption of urease, which expresses chemotactic activity for leukocytes by a mechanism not involving N-formylated oligopeptides.
Autoantibodies encoded by the most Jh-proximal human immunoglobulin heavy chain variable region gene.
Authors: T Logtenberg, F M Young, J H Van Es, F H Gmelig-Meyling, F W Alt
Journal: The Journal of Experimental Medicine (1989)

Little is known about the utilization of human Ig heavy chain variable gene segments (VH segments) in different B-lineage cell populations or in antibodies of particular specificity and function. We now demonstrate that human antibodies with Ig VH regions encoded by the most JH-proximal human VH segment (VH6) have specificities resembling those of autoantibodies present in sera of patients with systemic lupus erythematosus (e.g., anti-DNA and anticardiolipin). These specificities appear to be encoded by the germline VH6 gene because the activity was found in multiple independent VH6 antibodies in which the light chain varied with respect to isotype and V kappa subgroup. Features of CDR3 length and somatic mutation patterns in several VH6 antibodies suggested that they were selected by the immune system.
The effect of nasal tramazoline with dexamethasone in obstructive sleep apnoea patients
Authors: Ioannis Koutsourelakis, Aliki Minaritzoglou, Georgios Zakynthinos, Emmanouil Vagiakis, Spyros Zakynthinos
Journal: European Respiratory Journal (2013)

Although there is a strong correlation between oral/oro-nasal breathing and apnoea/hypopnoea index in patients with obstructive sleep apnoea and normal nasal resistance at wakefulness, it remains unknown whether the pharmacological prevention of potential nasal obstruction during sleep could decrease oral/oro-nasal breathing and increase nasal breathing and subsequently decrease the apnoea/hypopnoea index. This study evaluated the effect of a combination of a nasal decongestant with corticosteroid on breathing route pattern and apnoea/hypopnoea index. 21 patients with obstructive sleep apnoea (mean apnoea/hypopnoea index 31.1 events per hour) and normal nasal resistance at wakefulness were enrolled in a randomised crossover trial of 1 weeks’ treatment with nasal tramazoline and dexamethasone compared with 1 weeks’ treatment with nasal placebo. At the start and end of each treatment period, patients underwent nasal resistance measurement and overnight polysomnography with attendant measurement of breathing route pattern. Nasal tramazoline with dexamethasone was associated with decrease in oral/oro-nasal breathing epochs and concomitant increase in nasal breathing epochs, and mean decrease of apnoea/hypopnoea index by 21%. The change in nasal breathing epochs was inversely related to the change in apnoea/hypopnoea index (R s =0.78; p&lt;0.001). In conclusion, nasal tramazoline with dexamethasone in OSA patients with normal nasal resistance at wakefulness can restore the preponderance of nasal breathing epochs and modestly improve apnoea/hypopnoea index.
STUDIES OF BEHAVIOR AND THE METABOLISM OF INDOLE DERIVATIVES IN SCHIZOPHRENIA
Authors: NYLA J. COLE, ROGER B. ALLISON, MELVIN J. GORTATOWSKI, C. H. HARDIN BRANCH
Journal: American Journal of Psychiatry (1960)

1. Urinary indole excretion of spot 14 appears to depend upon the presence of certain bacterial flora in the gut. 2. When extraction of urine for chromatographic examination is carried out at pH 2.5, there appears to be no direct relationship between the appearance of indole 14 in the urine and the mental status classified as schizophrenia. 3. From the dietary drug studies reported, we would conclude that the probable source of this indole derivative that was examined (spot 14) is from bacterial flora acting upon certain dietary substances in the gut. As Benjamin, Kety(38, 9), and others have pointed out, the area of psychiatric research to date which has a rather fruitless history is the search for definite and discrete biological abnormalities as presumed etiological factors in the development of the schizophrenias. In the main, when rigid controls have been maintained and research design has allowed for examination of all possibilities, an expected primary causal relationship generally fades into being a secondary manifestation of factors intrinsic to the diagnosis of schizophrenia, such as dietary differences, institutionalization, behavioral differences, and so forth. This has been well illustrated recently by the fate, for example, of interest in ceruloplasmin(28, 39) and in phenolic acid excretion (40). In the author's opinion, the particular indole compound we have studied, i.e., "spot 14," can be included in the above category.
Interferon-β and interferon-λ signaling is not affected by interferon-induced refractoriness to interferon-α in vivo
Authors: Zuzanna Makowska, Francois H. T. Duong, Gaia Trincucci, David F. Tough, Markus H. Heim
Journal: Hepatology (2011)

Therapy of chronic hepatitis C with pegylated interferon α (pegIFN-α) and ribavirin achieves sustained virological responses in approximately half of the patients. Nonresponse to treatment is associated with constitutively increased expression of IFN-stimulated genes in the liver already before therapy. This activation of the endogenous IFN system could prevent cells from responding to therapeutically injected (peg)IFN-α, because prolonged stimulation of cells with IFN-α induces desensitization of the IFN signal transduction pathway. Whether all types of IFNs induce refractoriness in the liver is presently unknown. We therefore treated mice with multiple injections and different combinations of IFN-α, IFN-β, IFN-γ, and IFN-λ. Pretreatment of mice with IFN-α, IFN-β, and IFN-λ induced a strong expression of the negative regulator ubiquitin-specific peptidase 18 in the liver and gut. As a result, IFN-α signaling was significantly reduced when mice where reinjected 16 hours after the first injection. Surprisingly, both IFN-β and IFN-λ could activate the Janus kinase-signal transducer and activator of transcription (STAT) pathway and the expression of IFN-stimulated genes despite high levels of ubiquitin-specific peptidase 18. IFN-λ treatment of human liver biopsies ex vivo resulted in strong and maintained phosphorylation of STAT1, whereas IFN-α-induced STAT1 activation was transient. Conclusion: Contrary to the action of IFN-α, IFN-β, and IFN-λ signaling in the liver does not become refractory during repeated stimulation of the IFN signal transduction pathway. The sustained efficacy of IFN-β and IFN-λ could be an important advantage for the treatment patients who are nonresponders to pegIFN-α, through a preactivated endogenous IFN system. (HEPATOLOGY 2011;)
THE PATHOGENESIS OF THE HEMORRHAGIC DISEASES OF THE NEW-BORN
Authors: Evarts A. Graham
Journal: The Journal of Experimental Medicine (1912)

Those conditions of the new-born characterized by a hemorrhagic tendency, icterus, and fatty changes, are probably all syndromes which may occur as the result of a number of toxic agents. All of them, however, have been produced, in these experiments, by the action of a single experimental agent. Thus, a picture indistinguishable from that called Buhl's disease has been obtained by the use of chloroform, as have also the pictures known as Winckel's disease, melaena neonatorum, etc. Chloroform is not held to be the only substance that has this power. It stands rather as one member of a group of agents, the effects of which in general and in individual organs are similar to those caused by lack of oxygen. The essential features of these conditions have also been produced by direct asphyxiation of the fetus. The suggestion is therefore made that underlying all these symptoms and pathological complexes, there is a deficiency of oxidation, general, local, or selective, thus bringing this group of diseases into the general category of acute yellow atrophy of the liver, eclampsia, pernicious vomiting, cyclic vomiting, phosphorus poisoning, etc. In human beings, chloroform and asphyxia must, in many instances, be the determining causes. There remain, however, other cases in which different factors are to be sought.
Therapeutic Potential of Replication-Selective Oncolytic Adenoviruses on Cells from Familial and Sporadic Desmoid Tumors
Authors: Inge Peerlinck, Saeid Amini-Nik, Robin K. Phillips, Richard Iggo, Nicholas R. Lemoine, Sabine Tejpar, Georges Vassaux
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Constitutive activation of the Wnt signaling pathway is a hallmark of many cancers and has been associated with familial and sporadic desmoid tumors. The aim of the present study is to assess the therapeutic potential of oncolytic adenoviruses selectively replicating in cells in which the Wnt signaling pathway is active on primary cells from desmoid tumors. Experimental Design: Primary cells extracted from familial (n = 3) or sporadic (n = 3) desmoid tumors were cultured short term. Cancer cell survival and viral replication were measured in vitro upon infection with two different oncolytic adenoviruses targeting a constitutive activation of the Wnt signaling pathway. Adenoviral infectivity was also assessed. Results: Although cells extracted from one sporadic desmoid tumor responded very well to the oncolytic action of the adenoviruses (&amp;lt;20% of viable cells upon infection at a multiplicity of infection of 10), cells from two tumor samples were totally resistant to the viral action. Cells from the remaining samples showed intermediate sensitivity to the oncolytic viruses. These effects were correlated to the level of infectivity of the cells. Finally, in responder cells, evidences of viral replication was observed. Conclusions: Our experimental data suggest that the response of desmoid tumor cells to oncolytic adenovirus is neither correlated to the type of mutation activating the Wnt signaling pathway nor to the familial or sporadic nature of the tumor. In addition, they highlight the variability of infectivity of individual tumors and predict a great variability in the response to oncolytic adenoviruses.
In vivo and in vitro characterization of specific hyporeactivity to skin xenografts in mixed xenogeneically reconstituted mice (B10 + F344 rat----B10).
Authors: S T Ildstad, S M Wren, S O Sharrow, D Stephany, D H Sachs
Journal: The Journal of Experimental Medicine (1984)

Mixed xenogeneically reconstituted mice (F344 rat + C57BL/10Sn----C57BL/10Sn), which specifically retain F344 tail skin xenografts, were studied for the specificity of such hyporeactivity and for in vitro reactivity and immunocompetence. Survival of mixed reconstituted animals was excellent, without evidence for graft vs. host disease. Donor-type tail skin grafts were specifically prolonged (mean survival time = 80 d) in comparison with normal controls and syngeneically reconstituted animals. In vitro, such animals manifested specific hyporeactivity by mixed lymphocyte reaction and cell-mediated lympholysis to F344 rat and B10 cells, with normal response to third-party rat (Wistar-Furth) and mouse (B10.BR). Examination of lymphoid tissues with a fluorescence-activated cell sorter revealed low levels, if any, of donor-type cells detectable. This system offers a model for investigation of xenogeneic transplantation tolerance.
Premature pulmonary valve opening.
Authors: L S Wann, A E Weyman, J C Dillon, H Feigenbaum
Journal: Circulation (1977)

Premature opening of the pulmonary valve (opening independent of atrial or ventricular systole) was originally described in a case of sinus of Valsalva rupture into the right atrium. Since that time we have observed five additional cases in which the pulmonary valve opened prematurely. Entities encountered included: 1) constrictive pericarditis; 2) Loeffler's endocarditis; 3) Ebstein's anomaly with tricuspid regurgitation; 4) tricuspid regurgitation following tricuspid valvulectomy, and 5) pulmonary regurgitation accompanied by atrial septal defect. In the first two cases, premature pulmonary valve opening is felt to be due to restriction of diastolic filling of the right ventricle with subsequent early diastolic rise in pressure equalling or exceeding pulmonary artery diastolic pressure. In the latter three cases, the increased volume of blood entering the right ventricle again appeared to result in a rapid rise in initial right ventricular diastolic pressure and to produce premature opening of the pulmonary valve. Premature pulmonary valve opening, therefore, does not appear specific for any particular clinical entity but reflects the relative pressures in the right ventricle and pulmonary artery during diastole.
Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind phase 2 trial
Authors: Brian I Rini, Bohuslav Melichar, Takeshi Ueda, Viktor Grünwald, Mayer N Fishman, José A Arranz, Angel H Bair, Yazdi K Pithavala, Glen I Andrews, Dmitri Pavlov, Sinil Kim, Eric Jonasch
Journal: The Lancet Oncology (2013)
Caring for patients with HIV and AIDS in middle income countries
Authors: E. Van Praag, J. H Perriens
Journal: BMJ (1996)

Caring for patients with HIV and AIDS in middle income countries Preventing transmissionfrom mother to child isfar more cost effective than treating symptomatic infectionIn countries with rapidly growing economies, such as Thailand, Brazil, Malaysia, and South Africa, public spending on health has increased both'in relative and absolute terms.'It is hardly surprising that in these expanding markets new expensive medical technologies are being promoted as well.