tbuckley/cabot-search huggingface dataset:
Canine ventricular arrhythmias in the late myocardial infarction period. 8. Epicardial mapping of reentrant circuits.
Authors: N El-Sherif, R A Smith, K Evans
Journal: Circulation Research (1981)

We made simultaneous recordings from 48 bipolar electrodes to obtain epicardial isochronal maps during induced ventricular arrhythmias in dogs 3-5 days after ligation of the left anterior descending artery. There was strong evidence of a reentrant circuit (RC) that was discernible largely on the epicardial surface in 21% of ectopic beats that were analyzed. Epicardial recordings were of limited value in analyzing the arrhythmia in other beats. The reentrant circuit consisted of an arc of conduction block around which the activation front advanced in a circular fashion at slow but uneven speeds while the rest of the ventricle was activated by radial spread. The arc of conduction block around which the RC was formed was usually functional in nature, since the same area of myocardium was excitable at relatively long cardiac cycle lengths. Both the length of the arc of conduction block which defines the length of the reentrant circuit and the degree of conduction delay were crucial factors for the occurrence of reentry. A premature beat that initiated reentry resulted in a longer arc of conduction block and slower conduction compared to one that failed to induce reentry.
Acute gastrointestinal haemorrhage in anticoagulated patients: diagnoses and response to endoscopic treatment.
Authors: C P Choudari, C Rajgopal, K R Palmer
Journal: Gut (1994)

The underlying diagnosis and clinical course of 52 patients who presented with severe acute gastrointestinal haemorrhage while taking the anticoagulant warfarin is reviewed. A bleeding site was identified in 83% of cases, only slightly fewer than the 92% found in a control of group of 710 patients not taking warfarin who presented in the same four year period. The degree or duration of anticoagulation was unrelated to the frequency of establishing a diagnosis. The commonest diagnosis was peptic ulcer (25 cases) and endoscopic treatment by injection or heater probe was attempted in 23 of these. The outcome in this subgroup was compared with that in 50 closely matched control subjects who had similar risk factors for rebleeding from peptic ulcer. Permanent haemostasis was achieved in (91%) of the anticoagulated and in 92% of the control patients. There were no complications related to endoscopy. Patients who present with acute gastrointestinal haemorrhage while taking warfarin usually bleed from mucosal disease. They should be endoscoped after resuscitation and those with major bleeding from a peptic ulcer should be offered endoscopic treatment.
Cells in bone marrow and in T cell colonies grown from bone marrow can suppress generation of cytotoxic T lymphocytes directed against their self antigens.
Authors: S Muraoka, R G Miller
Journal: The Journal of Experimental Medicine (1980)

Both normal mouse bone marrow and cells from T cell-containing colonies grown in vitro from normal bone marrow contain cells which can specifically suppress the development of cytotoxic T lymphocytes capable of recognizing alloantigens on the bone marrow or colony cells. Suppression, as assessed by reduction in cytotoxic activity, is produced by adding bone marrow or colony cells to mixed lymphocyte reactions between lymph node responder cells and irradiated histoincompatible spleen stimulator cells. The cytotoxic activity is reduced if the added bone marrow or colony cells are syngeneic or semisyngeneic to the stimulator cells but not if they are allogeneic. Suppression results from a reduction in the number of cytotoxic lymphocyte precursor cells activated in the cultures. The suppressor cells in bone marrow are radiation sensitive and Thy-1 negative; those in colonies grown from bone marrow are radiation resistant and Thy-1 positive.
Pain and Quality of Life After Treatment in Patients With Locally Recurrent Rectal Cancer
Authors: Nestor F. Esnaola, Scott B. Cantor, Margo L. Johnson, Attiqa N. Mirza, Alexander R. Miller, Steven A. Curley, Christopher H. Crane, Charles S. Cleeland, Nora A. Janjan, John M. Skibber
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Because survival in patients with locally recurrent rectal cancer (LRRC) is limited, pain control and quality of life (QOL) are important parameters. The purpose of this study was to assess the prevalence of posttreatment pain and QOL of patients with LRRC treated with nonsurgical palliation or resection and identify predictors of poor outcome. PATIENTS AND METHODS: Posttreatment pain severity and QOL were prospectively assessed in 45 patients with LRRC using the Brief Pain Inventory and Functional Assessment of Cancer Therapy–Colorectal questionnaire. RESULTS: Fifteen patients received nonsurgical palliation, and 30 patients underwent resection of their pelvic tumors. There was a significant association between higher posttreatment pain scores and worse QOL (P &lt; .001). Patients treated with nonsurgical palliation reported moderate to severe pain beyond the third month of treatment. Resected patients reported comparable levels of pain during the first 3 postoperative years, particularly after bony resections; long-term survivors (beyond 3 years), however, reported minimal pain and good QOL. Female sex, pelvic/sciatic pain at presentation, total pelvic exenteration, and bony resection were associated with higher rates of moderate to severe posttreatment pain (P = .04, P &lt; .001, P = .04, and P = .02, respectively). Pain at presentation was an independent predictor of posttreatment pain (odds ratio, 7.4 [95% confidence interval, 1.8 to 30.3]; P = .006). CONCLUSION: Patients with LRRC treated with nonsurgical palliation or resection experience significant levels of pain after treatment. Close posttreatment pain monitoring is warranted in patients presenting with pelvic pain, and more aggressive pain management strategies may improve posttreatment QOL.
PLC-γ2 is essential for formation and maintenance of memory B cells
Authors: Masaki Hikida, Stefano Casola, Noriko Takahashi, Tomohiro Kaji, Toshitada Takemori, Klaus Rajewsky, Tomohiro Kurosaki
Journal: The Journal of Experimental Medicine (2009)

Resting antigen-experienced memory B cells are thought to be responsible for the more rapid and robust antibody responses after antigen reencounter, which are the hallmark of memory humoral responses. The molecular basis for the development and survival of memory B cells remains largely unknown. We report that phospholipase C (PLC) γ2 is required for efficient formation of germinal center (GC) and memory B cells. Moreover, memory B cell homeostasis is severely hampered by inducible loss of PLC-γ2. Accordingly, mice with a conditional deletion of PLC-γ2 in post-GC B cells had an almost complete abrogation of the secondary antibody response. Collectively, our data suggest that PLC-γ2 conveys a survival signal to GC and memory B cells and that this signal is required for a productive secondary immune response.
Effect of acute changes in glomerular filtration rate on Na+/H+ exchange in rat renal cortex.
Authors: D A Maddox, S M Fortin, A Tartini, W D Barnes, F J Gennari
Journal: Journal of Clinical Investigation (1992)

Studies were undertaken in Munich-Wistar rats to assess the influence of changes in filtered bicarbonate (FLHCO3), induced by changes in GFR, on Na+/H+ exchange activity in renal brush border membrane vesicles (BBMV). Whole-kidney and micropuncture measurements of GFR, FLHCO3, and whole-kidney and proximal tubule HCO3 reabsorption (APRHCO3) were coupled with BBMV measurements of H+ gradient-driven 22Na+ uptake in each animal studied. 22Na+ uptake was measured at three Na+ concentration gradients to allow calculation of Vmax and Km for Na+/H+ exchange. GFR was varied by studying animals under conditions of hydropenia, plasma repletion, and acute plasma expansion. The increase in GFR, FLHCO3, and APRHCO3 induced by plasma administration correlated directly with an increase in the Vmax for Na+/H+ exchange in BBMV. The Km for sodium was unaffected. In the plasma-expanded rats, the Vmax for Na+/H+ exchange was 22% greater than in the hydropenic rats (P less than 0.025) whereas APRHCO3 was 86% greater (P less than 0.001). These results indicate that increases in FLHCO3, induced by acute increases in GFR, stimulate Na+/H+ exchange activity in proximal tubular epithelium. This stimulation is a mechanism which can, in part, account for the delivery dependence of proximal bicarbonate reabsorption.
Neuromuscular blockade with acute respiratory failure in a patient receiving cibenzoline
Authors: T. Similowski, C. Straus, V. Attali, F. Girard, F. Philippe, G. Deray, D. Thomas, J. P. Derenne
Journal: Thorax (1997)

Cibenzoline is a class Ic antiarrhythmic agent that can be used to treat supraventricular arrhythmias. A case is reported of cibenzoline overdose in a patient with impaired renal function, leading not only to the usual cardiac and metabolic symptoms (bradycardia and hypoglycaemia), but also to a myastheniform syndrome with acute respiratory failure. Neuromuscular blockade was demonstrated by repetitive supramaximal stimulation of the median nerve, and diaphragmatic involvement was evidenced by applying the same protocol to the phrenic nerve. Muscle strength recovered as serum cibenzoline levels decreased, allowing the patient to be weaned from the ventilator. This observation suggests that cibenzoline, like other antiarrhythmic agents, can be responsible for neuromuscular blockade, and should therefore be used with caution in patients with neuromuscular and respiratory diseases or with impaired renal function.
The Effects of Regressive ECT with Process Schizophrenics
Authors: LUIS G. MURILLO, JOHN E. EXNER
Journal: American Journal of Psychiatry (1973)

An experimental group of 32 process schizophrenics was treated with regressive ECT, while a control group of 2l patients was treated with ataraxic drugs and psychotherapy. All patients were evaluated at admission and at or after discharge, using four sources of evaluation: self-ratings, psychological tests, relatives' ratings, and ratings by referring therapists. Statistical analysis of 55 variables indicated that the two groups were essentially equivalent at admission but showed significant differences on 28 of the 55 variables after discharge. All of the variables favored the experimental group treated with regressive ECT.
Sympathetic Stimulation of Adult Cardiomyocytes Requires Association of AKAP5 With a Subpopulation of L-Type Calcium Channels
Authors: C. Blake Nichols, Charles F. Rossow, Manuel F. Navedo, Ruth E. Westenbroek, William A. Catterall, Luis F. Santana, G. Stanley McKnight
Journal: Circulation Research (2010)

Sympathetic stimulation of the heart increases the force of contraction and rate of ventricular relaxation by triggering protein kinase (PK)A-dependent phosphorylation of proteins that regulate intracellular calcium. We hypothesized that scaffolding of cAMP signaling complexes by AKAP5 is required for efficient sympathetic stimulation of calcium transients.We examined the function of AKAP5 in the β-adrenergic signaling cascade.We used calcium imaging and electrophysiology to examine the sympathetic response of cardiomyocytes isolated from wild type and AKAP5 mutant animals. The β-adrenergic regulation of calcium transients and the phosphorylation of substrates involved in calcium handling were disrupted in AKAP5 knockout cardiomyocytes. The scaffolding protein, AKAP5 (also called AKAP150/79), targets adenylyl cyclase, PKA, and calcineurin to a caveolin 3-associated complex in ventricular myocytes that also binds a unique subpopulation of Ca(v)1.2 L-type calcium channels. Only the caveolin 3-associated Ca(v)1.2 channels are phosphorylated by PKA in response to sympathetic stimulation in wild-type heart. However, in the AKAP5 knockout heart, the organization of this signaling complex is disrupted, adenylyl cyclase 5/6 no longer associates with caveolin 3 in the T-tubules, and noncaveolin 3-associated calcium channels become phosphorylated after β-adrenergic stimulation, although this does not lead to an enhanced calcium transient. The signaling domain created by AKAP5 is also essential for the PKA-dependent phosphorylation of ryanodine receptors and phospholamban.These findings identify an AKAP5-organized signaling module that is associated with caveolin 3 and is essential for sympathetic stimulation of the calcium transient in adult heart cells.
Oral Administration of Gemcitabine in Patients with Refractory Tumors: A Clinical and Pharmacologic Study
Authors: Stephan A. Veltkamp, Robert S. Jansen, Sophie Callies, Dick Pluim, Carla M. Visseren-Grul, Hilde Rosing, Susanne Kloeker-Rhoades, Valerie A.M. Andre, Jos H. Beijnen, Christopher A. Slapak, Jan H.M. Schellens
Journal: Clinical Cancer Research (2008)

To determine the toxicity, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of oral gemcitabine (2',2'-difluorodeoxycytidine; dFdC) in patients with cancer.Patients with advanced or metastatic cancer refractory to standard therapy were eligible. Gemcitabine was administered p.o. starting at 1 mg once daily using dose escalation with three patients per dose level. Patients received one of two dosing schemes: (a) once daily dosing for 14 days of a 21-day cycle or (b) every other day dosing for 21 days of a 28-day cycle. Pharmacokinetics were assessed by measuring concentrations of dFdC and 2',2'-difluorodeoxyuridine (dFdU) in plasma and gemcitabine triphosphate in peripheral blood mononuclear cells, and pharmacodynamics by measuring the effect on T-cell proliferation.Thirty patients entered the study. Oral gemcitabine was generally well-tolerated. The maximum tolerated dose was not reached. Mainly moderate gastrointestinal toxicities occurred except for one patient who died after experiencing grade 4 hepatic failure during cycle two. One patient with a leiomyosarcoma had stable disease during 2 years and 7 months. Systemic exposure to dFdC was low with an estimated bioavailability of 10%. dFdC was highly converted to dFdU, probably via first pass metabolism and dFdU had a long terminal half-life ( approximately 89 h). Concentrations of dFdCTP in peripheral blood mononuclear cells were low, but high levels of gemcitabine triphosphate, the phosphorylated metabolite of dFdU, were detected.Systemic exposure to oral gemcitabine was low due to extensive first-pass metabolism to dFdU. Moderate toxicity combined with hints of activity warrant further investigation of the concept of prolonged exposure to gemcitabine.
The Maryland Experience and a Practical Proposal to Expand Existing Models in Ambulatory Primary Care
Authors: W. Anthony Riley
Journal: JAMA (1991)

Two unique models for caring for the uninsured and underinsured are operating in Maryland. The first is a group practice, primary care model with a unique ambulatory Medicare waiver that has had a positive impact on patients and physicians. The second is a financial model--an all-payer prospective rate-setting system for all critical care inpatient hospitals that, during a 13-year period from 1977 through 1989, has saved the citizens of the state approximately $5.361 billion, has allowed hospitals to provide $1.657 billion of charity care and bad debts, and has earned $517 million in net profits. The reasons for the success of each of the models are discussed and form the basis for a practical and politically feasible proposal: merge the best aspects of each model into an ambulatory primary care-based model financed through an all-payer prospective charge system.
Comparison of intravenous gamma globulin and a monoclonal anti-Fc receptor antibody as inhibitors of immune clearance in vivo in mice.
Authors: R J Kurlander, J Hall
Journal: Journal of Clinical Investigation (1986)

Fc-receptor-mediated clearance and nonspecific phagocytic clearance were assessed after the infusion of monomeric human IgG, heat-aggregated human IgG, and a monoclonal anti-mouse macrophage FcII receptor antibody (2.4G2) into normal mice. Each agent blocked Fc-receptor function in vivo, but 2.4G2 was much more potent per microgram than the other agents. Monomeric IgG in blocking doses did not affect other aspects of immune function. In contrast, aggregated IgG, and to a lesser extent, 2.4G2 reduced serum complement levels. In addition, these agents also caused moderate reductions in nonspecific phagocytic function. Monoclonal anti-mouse macrophage C3bi receptor antibody (Mac-1), another monoclonal antibody which binds to macrophage CR3 receptors without interfering with Fc-receptor function, also reduced serum complement and inhibited nonspecific phagocytic function. Complement depletion alone (produced by infusion of cobra venom factor) could not account for the observed changes in Fc receptor or nonspecific phagocytic function. We conclude that both monomeric IgG and anti-Fc-receptor antibodies can markedly inhibit Fc-receptor function in vivo; however, the pattern of physiologic changes produced by these agents differs.
Argonaute 2 in dopamine 2 receptor–expressing neurons regulates cocaine addiction
Authors: Anne Schaefer, Heh-In Im, Morten T. Venø, Christie D. Fowler, Alice Min, Adam Intrator, Jørgen Kjems, Paul J. Kenny, Donal O’Carroll, Paul Greengard
Journal: The Journal of Experimental Medicine (2010)

Cocaine is a highly addictive drug that exerts its effects by increasing the levels of released dopamine in the striatum, followed by stable changes in gene transcription, mRNA translation, and metabolism within medium spiny neurons in the striatum. The multiple changes in gene and protein expression associated with cocaine addiction suggest the existence of a mechanism that facilitates a coordinated cellular response to cocaine. Here, we provide evidence for a key role of miRNAs in cocaine addiction. We show that Argonaute 2 (Ago2), which plays an important role in miRNA generation and execution of miRNA-mediated gene silencing, is involved in regulation of cocaine addiction. Deficiency of Ago2 in dopamine 2 receptor (Drd2)–expressing neurons greatly reduces the motivation to self-administer cocaine in mice. We identified a distinct group of miRNAs that is specifically regulated by Ago2 in the striatum. Comparison of miRNAs affected by Ago2 deficiency with miRNAs that are enriched and/or up-regulated in Drd2-neurons in response to cocaine identified a set of miRNAs that are likely to play a role in cocaine addiction.
Abstract 1864: Reptin as a tumor-associated antigen of epithelial ovarian cancer
Authors: Eun-ju Lee, Hanbyoul Cho, Ha-Yeon Shin, Wookyeom Yang, Hyunja Kwon, Sol Kim, Jae-Hoon Kim
Journal: Cancer Research (2014)

Abstract Background: Reptin is also known as RuvBl2, Tip48, TIP49b, ECP51 and CGI-46, is a member of AAA+ (ATPases associated with diverse cellular activities) superfamily. Reptin is associated with cell viability and development of S. cerevisiae, D. melanogaster, X. laevis, or D. rerio has a lot of functions including transcriptional regulation, DNA damage repair and telomerase activity. Self-reactive IgG autoantibodies are present on human sera.Each self-reactive IgG autoantibody derived from pre- and post-treatment of ovarian cancer patients is competitively combined with cancer tissue gotten during the operation, self-reactive IgG autoantibodies bound to tumor antigens. As a result, self-reactive IgG autoantibodies may be decreased after treatment. In this study, we have identified and investigated the function of Reptin as an available therapeutic biomarker for ovarian cancer using difference of self-reactive IgG autoantibody amounts. Method: We carried out the two-dimensional differential gel electrophoresis analysis of immunoprecipitated tumor antigens (2D-DITA) to compare with expression level of autoantibodies in pre- and post-treatment sera of 14 ovarian cancer patients. Autoantibody differentiated between pre- and post-treatment sera was identified by MALDI-TOF. We performed qRT-PCR with 8 human ovarian surface epitheliums (HOSEs) and 14 ovarian cancer cell lines for validation studies. Reptin was also detected in other ovarian cancer tissues by immunohistochemistry (IHC). We constructed SKOV-3 cell line for overexpression Reptin using lentiviral system. For investigating function of Reptin, we performed proliferation, wound healing, and invasion assay. Results: We identified Reptin as a tumor-associated antigen of epithelial ovarian cancer. Relative mRNA level of Reptin showed higher levels in ovarian cancer cell lines than in HOSEs. Reptin protein levels were significantly upregulated in ovarian cancer tissues than normal, benign, and borderline ovarian tumors. In SKOV-3 cells, overexpression of Reptin induced inhibition of cell proliferation (P&amp;lt;0.0001), migration and invasion (P&amp;lt;0.0001). Conclusion: Our results demonstrate that Reptin is a tumor -associated antigen of ovarian cancer, i.e. tumor suppressor. Citation Format: Eun-ju Lee, Hanbyoul Cho, Ha-Yeon Shin, Wookyeom Yang, Hyunja Kwon, Sol Kim, Jae-Hoon Kim. Reptin as a tumor-associated antigen of epithelial ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1864. doi:10.1158/1538-7445.AM2014-1864
Treatment of chronic inflammatory diseases with implantable medical devices
Authors: R. J. Zitnik
Journal: Annals of the Rheumatic Diseases (2011)

Implantable medical devices are finding increasing use in the treatment of diseases traditionally targeted with drugs. It is well established that the cholinergic anti-inflammatory pathway serves as a physiological regulator of inflammatory responses, but stimulation of this pathway therapeutically by electrical stimulation of the vagus nerve can also diminish excessive or dysregulated states of inflammation. Recent data from a wide variety of animal models, as well as evidence of reduced vagal tone in rheumatoid arthritis and other inflammatory diseases, support the rationale for, and feasibility of, developing implantable vagal nerve stimulation devices to treat chronic inflammation in humans.
Molecular characterization of antibodies bearing Id-460. II. Molecular basis for Id-460 expression.
Authors: E A Dzierzak, P Brodeur, T Marion, C A Janeway, A Bothwell
Journal: The Journal of Experimental Medicine (1985)

Id-460+ immunoglobulins can be induced in vivo by immunization with dinitrophenyl (DNP) or P. pneumotropica and form two nonoverlapping groups of antibodies with respect to antigen binding specificity. In this study, using Id-460+ antibodies of differing antigen binding specificities, we compared on the molecular genetic level the five gene segment combinations (VH, DH, JH, VL, and JL) that encode the variable regions of these idiotype-positive immunoglobulins. The Id-460 determinant appears to be a conformational or combinatorial determinant encoded by VH460 and VK1 crosshybridizing genes. DH, JH, and JK gene segments appear to have no measurable effect upon expression of Id-460. Finally, antigen binding specificity does not appear to simply localize to any particular gene segment but may in part be the result of somatic mutation and/or VDJH junctional sequences, whose length correlates roughly with antigen binding specificity.