tbuckley/cabot-search huggingface dataset:
Idiotypic cross-reactivity between antibodies of different specificities.
Authors: R Karol, M Reichlin, R W Noble
Journal: The Journal of Experimental Medicine (1978)

Cross-idiotypic specificity has been demonstrated between antibody populations of different specificities using antibodies directed toward human sickle cell hemoglobin (HbS). A site-specific antibody directed toward the beta6-position of HbS, anti-Val, was used to elicit an anti-idiotypic response in rabbits. Using this anti-idiotypic serum, idiotypic cross-reactivity was demonstrated between antibody populations that bind to human adult hemoglobin (HbA). It was demonstrated that in the case of the goat antibodies, these idiotypically cross-reacting antibodies are directed towards the beta6-position of the hemoglobin molecule. However, they differ in their specificity, binding to this site on HbA, whereas anti-Val binds only to HbS. The sheep antibody populations directed toward HbS differ qualitatively from those of the goat. Using rabbit anti-idiotypic serum specific for sheep anti-Val, cross-reactivity could be demonstrated with antibodies directed toward the alpha-chain of the hemoglobin molecule, as well as the beta-chain. There was also a low level of cross-reactivity with antibodies from a goat immunized with HbA.
Effects of Electrical Shocks on Ca <sub>i</sub> <sup>2+</sup> and V <sub>m</sub> in Myocyte Cultures
Authors: Vladimir G. Fast, Eric R. Cheek, Andrew E. Pollard, Raymond E. Ideker
Journal: Circulation Research (2004)

Changes in intracellular calcium concentration (DeltaCa(i)2+) induced by electrical shocks may play an important role in defibrillation, but high-resolution DeltaCa(i)2+ measurements in a multicellular cardiac tissue and their relationship to corresponding Vm changes (DeltaVm) are lacking. Here, we measured shock-induced DeltaCa(i)2+ and DeltaV(m) in geometrically defined myocyte cultures. Cell strands (width=0.8 mm) were double-stained with Vm-sensitive dye RH-237 and a low-affinity Ca(i)2+-sensitive dye Fluo-4FF. Shocks (E approximately 5 to 40 V/cm) were applied during the action potential plateau. Shocks caused transient Ca(i)2+ decrease at sites of both negative and positive DeltaV(m). Similar Ca(i)2+ changes were observed in an ionic model of adult rat myocytes. Simulations showed that the Ca(i)2+ decrease at sites of DeltaV+m was caused by the outward flow of I(CaL) and troponin binding; at sites of DeltaV-m it was caused by inactivation of I(CaL) combined with extrusion by Na-Ca exchanger and troponin binding. The important role of I(CaL) was supported by experiments in which application of nifedipine eliminated Ca(i)2+ decrease at DeltaV+m sites. Largest DeltaCa(i)2+ were observed during shocks of approximately 10 V/cm causing simple monophasic DeltaV(m). Shocks stronger than approximately 20 V/cm caused smaller DeltaCa(i)2+ and postshock elevation of diastolic Ca(i)2+. This was paralleled with occurrence of biphasic negative DeltaVm that indicated membrane electroporation. Thus, these data indicate that shocks transiently decrease Ca(i)2+ at sites of both DeltaV-m and DeltaV+m. Outward flow of I(CaL) plays an important role in Ca(i)2+ decrease in the DeltaV+m areas. Very strong shocks caused smaller negative DeltaCa(i)2+ and postshock elevation of diastolic Ca(i)2+, likely caused by membrane electroporation.
Emergence of Domestically Acquired Ceftriaxone-Resistant &lt;EMPH TYPE="ITAL"&gt;Salmonella&lt;/EMPH&gt; Infections Associated With AmpC β-Lactamase
Authors: Eileen F. Dunne
Journal: JAMA (2000)

ACH YEAR, AN ESTIMATED 1.4 MILlion persons in the United States are infected with Salmonella. 1 Many of these infections occur in children; 7% of the 2840 cultureconfirmed Salmonella infections reported to the Centers for Disease Control and Prevention in 1998 through Foodborne Diseases Active Surveillance Network (FoodNet) occurred in persons aged 18 years or younger. 2 Although most Salmonella infections result in mild-to-moderate gastroenteritis, which resolves spontaneously, systemic infections, including bacteremia and meningitis, also occur. 3Invasive infections commonly occur in children, particularly in infants. 4Ten percent of culture-confirmed infec-tions from blood or the central nervous system reported to the Centers for Disease Control and Prevention were in infants younger than 1 year.Furthermore, an estimated 595 persons die each year as a consequence of Salmonella infections. 1 Antimicrobial agents are commonly used empirically for the treatment of patients with moderate-to-severe diar-
Components of the Ligand for a Ni++ Reactive Human T Cell Clone
Authors: Linh Lu, Jörg Vollmer, Corinne Moulon, Hans Ulrich Weltzien, Philippa Marrack, John Kappler
Journal: The Journal of Experimental Medicine (2003)

The major histocompatibility complex (MHC) restriction element for a human Ni2+ reactive T cell, ANi-2.3, was identified as DR52c. A series of experiments established that the functional ligand for this T cell was a preformed complex of Ni2+ bound to the combination of DR52c and a specific peptide that was generated in human and mouse B cells, but not in fibroblasts nor other antigen processing–deficient cells. In addition, ANi-2.3 recognition of this complex was dependent on His81 of the MHC β chain, suggesting a role for this amino acid in Ni2+ binding to MHC. We propose a general model for Ni2+ recognition in which βHis81 and two amino acids from the NH2-terminal part of the MHC bound peptide coordinate Ni2+ which then interacts with some portion of the Vα CDR1 or CDR2 region.
Dofequidar Fumarate (MS-209) in Combination With Cyclophosphamide, Doxorubicin, and Fluorouracil for Patients With Advanced or Recurrent Breast Cancer
Authors: Toshiaki Saeki, Tadashi Nomizu, Masakazu Toi, Yoshinori Ito, Shinzaburo Noguchi, Tadashi Kobayashi, Taro Asaga, Hironobu Minami, Naohito Yamamoto, Kenjiro Aogi, Tadashi Ikeda, Yasuo Ohashi, Wakao Sato, Takashi Tsuruo
Journal: Journal of Clinical Oncology (2006)

To evaluate the efficacy and tolerability of dofequidar plus cyclophosphamide, doxorubicin, and fluorouracil (CAF) therapy in comparison with CAF alone, in patients with advanced or recurrent breast cancer. Dofequidar is a novel, orally active quinoline derivative that reverses multidrug resistance.In this randomized, double-blind, placebo-controlled trial, patients were treated with six cycles of CAF therapy: 28 days/cycle, with doxorubicin (25 mg/m2) and fluorouracil (500 mg/m2) administered on days 1 and 8 and cyclophosphamide (100 mg orally [PO]) administered on day 1 through 14. Patients received dofequidar (900 mg PO) 30 minutes before each dose of doxorubicin. Primary end point was overall response rate (ORR; partial or complete response). In total, 221 patients were assessable.ORR was 42.6% for CAF compared with 53.1% for dofequidar + CAF, a 24.6% relative improvement and 10.5% absolute increase (P = .077). There was a trend for prolonged progression-free survival (PFS; median 241 days for CAF v 366 days for dofequidar + CAF; P = .145). In retrospectively defined subgroups, significant improvement in PFS in favor of dofequidar was observed in patients who were premenopausal, had no prior therapy, and were stage IV at diagnosis with an intact primary tumor. Except for neutropenia and leukopenia, there was no statistically significant excess of grade 3/4 adverse events compared with CAF. Treatment with dofequidar did not affect the plasma concentration of doxorubicin.Dofequidar + CAF was well tolerated and is suggested to have efficacy in patients who had not received prior therapy.
Characteristics of Shock Following Acute Reduction of Cardiac Output in Dogs
Authors: FREDERICK H. MEYERS, JOSEPH C. SCHOOLAR, RICHARD R. OVERMAN
Journal: Circulation Research (1954)

A state of shock followed the acute reduction of cardiac output caused by injection of a necrotizing solution into the myocardium. Decrease in blood pressure, decrease in circulating plasma volume, increase in hematocrit readings and the effect of re-expansion of the plasma volume established the similarity of this state to other forms of shock. Pulmonary blood volume decreased concurrently with cardiac output and effective plasma volume.
Pharmacokinetic and Pharmacodynamic Analysis of Circulating Biomarkers of Anti-NRP1, a Novel Antiangiogenesis Agent, in Two Phase I Trials in Patients with Advanced Solid Tumors
Authors: Yan Xin, Jessica Li, Jenny Wu, Rashell Kinard, Colin D. Weekes, Amita Patnaik, Patricia LoRusso, Rainer Brachmann, Raymond K. Tong, Yibing Yan, Ryan Watts, Shuang Bai, Priti S. Hegde
Journal: Clinical Cancer Research (2012)

MNRP1685A is a monoclonal antibody to neuropilin-1 (NRP1). We evaluated blood-based pharmacodynamic biomarkers of MNRP1685A in two phase I studies to assess exposure/response relationships to inform target dose and regimen selection.The phase I studies evaluated escalating doses of MNRP1685A as a single agent or in combination with bevacizumab. Plasma placental growth factor (PlGF), VEGF, and circulating NRP1 (cNRP1) were evaluated at multiple time points using meso-scale discovery (MSD) assays and ELISA, respectively. Plasma PlGF was also measured in a phase I/II trial of bevacizumab in metastatic breast cancer (AVF0776). The association between PlGF and MNRP1685A dose was described by a sigmoid E(max) model. cNRP1 and MNRP1685A PK profiles were described using a two-target quasi-steady state (QSS) model.A dose- and time-dependent increase in plasma PlGF and cNRP1 was observed in all patients treated with MNRP1685A. PK/PD analysis showed that bevacizumab and MNRP1685A had an additive effect in elevating PlGF. Predictions based on the two-target QSS model showed that the free drug concentration to maintain greater than 90% saturation of membrane NRP1 (mNRP1) and cNRP1 is about 8 μg/mL.These data show that MNRP1685A inhibits the VEGF pathway in humans as assessed by an increase in plasma PlGF. MNRP1685A seems to enhance bevacizumab-mediated VEGF pathway blockade, as showed by an increase in the magnitude of PlGF elevation when combined with bevacizumab. PK/PD analysis of biomarkers in the phase I population allowed identification of doses at which apparent maximal pathway modulation was observed.
Herpes gestationis autoantibodies recognize a 180-kD human epidermal antigen.
Authors: L H Morrison, R S Labib, J J Zone, L A Diaz, G J Anhalt
Journal: Journal of Clinical Investigation (1988)

Herpes gestationis (HG) is a putative autoimmune bullous dermatosis of pregnancy which shares many findings with bullous pemphigoid (BP), a disease of the elderly. This study identifies for the first time the antigen detected by HG autoantibodies and compares it with that recognized by BP autoantibodies. Sera from 16 HG and 17 BP patients, and from normal pregnant women were evaluated by immunofluorescent (IF) studies and immunoblotted against human epidermal extracts. 89% of HG sera with circulating antibodies by IF recognized a 180-kD protein by immunoblotting. 71% of BP sera recognized a 240-kD band, but 47% detected a 180-kD protein that comigrated with the antigen detected by HG sera. None of the control sera recognized any specific bands. These findings suggest that the 180-kD epidermal protein may be the antigen detected by the HG factor and they also define immunologic similarities between HG and BP.
Transcriptomics-based screen for genes induced by flagellin and repressed by pathogen effectors identifies a cell wall-associated kinase involved in plant immunity
Authors: Hernan G Rosli, Yi Zheng, Marina A Pombo, Silin Zhong, Aureliano Bombarely, Zhangjun Fei, Alan Collmer, Gregory B Martin
Journal: Genome biology (2013)

Microbe-associated molecular patterns, such as those present in bacterial flagellin, are powerful inducers of the innate immune response in plants. Successful pathogens deliver virulence proteins, termed effectors, into the plant cell where they can interfere with the immune response and promote disease. Engineering the plant immune system to enhance disease resistance requires a thorough understanding of its components. We describe a high-throughput screen, using RNA sequencing and virus-induced gene silencing, to identify tomato genes whose expression is enhanced by the flagellin microbe-associated molecular pattern flgII-28, but reduced by activities of the Pseudomonas syringae pv. tomato (Pst) type III effectors AvrPto and AvrPtoB. Gene ontology terms for this category of Flagellin-induced repressed by effectors (FIRE) genes showed enrichment for genes encoding certain subfamilies of protein kinases and transcription factors. At least 25 of the FIRE genes have been implicated previously in plant immunity. Of the 92 protein kinase-encoding FIRE genes, 33 were subjected to virus-induced gene silencing and their involvement in pattern-triggered immunity was tested with a leaf-based assay. Silencing of one FIRE gene, which encodes the cell wall-associated kinase SlWAK1, compromised the plant immune response resulting in increased growth of Pst and enhanced disease symptoms. Our transcriptomic approach identifies FIRE genes that represent a pathogen-defined core set of immune-related genes. The analysis of this set of candidate genes led to the discovery of a cell wall-associated kinase that participates in plant defense. The FIRE genes will be useful for further elucidation of the plant immune system.
Research Advance Directives: Protection or Obstacle?
Authors: Palaniappan Muthappan, Heidi Forster, David Wendler
Journal: American Journal of Psychiatry (2005)

This study assessed how many adults completed a research advance directive and the preferences indicated on the completed forms.The authors analyzed all 2,371 adults admitted as inpatients to the NIH Clinical Center from March 14 to Sept. 13, 2000.Overall, 11% of adult inpatients completed a research advance directive. Of those who specified preferences, 13% were not willing to participate in future research should they become unable to consent, 76% were willing to participate in research that might help them, 49% were willing to participate in research that would not help them and posed minimal risk, and 9% were willing to participate in research that would not help them and posed greater than minimal risk.Proposals to allow cognitively impaired adults to participate in research only with a formal advance directive could block important research. More flexible approaches should be considered to protect these individuals.
The time course of in vivo recovery of transverse strain in high-stress tendons following exercise
Authors: Scott C Wearing, James E Smeathers, Sue L Hooper, Simon Locke, Craig Purdam, Jill L Cook
Journal: British Journal of Sports Medicine (2013)

To evaluate the time course of the recovery of transverse strain in the Achilles and patellar tendon following a bout of resistance exercise.Seventeen healthy adults underwent sonographic examination of the right patellar (n=9) and Achilles (n=8) tendons immediately prior to and following 90 repetitions of weight-bearing quadriceps and gastrocnemius-resistance exercise performed against an effective resistance of 175% and 250% body weight, respectively. Sagittal tendon thickness was determined 20 mm from the enthesis and transverse strain, as defined by the stretch ratio, was repeatedly monitored over a 24 h recovery period.Resistance exercise resulted in an immediate decrease in Achilles (t7=10.6, p<0.01) and patellar (t8=8.9, p<0.01) tendon thickness, resulting in an average transverse stretch ratio of 0.86±0.04 and 0.82±0.05, which was not significantly different between tendons. The magnitude of the immediate transverse strain response, however, was reduced with advancing age (r=0.63, p<0.01). Recovery in transverse strain was prolonged compared with the duration of loading and exponential in nature. The average primary recovery time was not significantly different between the Achilles (6.5±3.2 h) and patellar (7.1±3.2 h) tendons. Body weight accounted for 62% and 64% of the variation in recovery time, respectively.Despite structural and biochemical differences between the Achilles and patellar tendon, the mechanisms underlying transverse creep recovery in vivo appear similar and are highly time dependent. These novel findings have important implications concerning the time required for the mechanical recovery of high-stress tendons following an acute bout of exercise.
Lymphangiogenesis and Cancer
Authors: Kari Alitalo, Suresh Mohla, Erkki Ruoslahti
Journal: Cancer Research (2004)

The presence of tumor cells in lymph nodes (LNs) is a sign that metastatic spread of cancer has occurred, and it also signals poor prognosis for patients with cancer. However, it is uncertain whether the lymphatic vasculature is a route for the further dissemination of tumor cells to distant organs
Introducing Psychiatry to Rural Physicians in China: An Innovative Education Project
Authors: Samuel F. Law, Pozi Liu, Brian D. Hodges, Wes Shera, Xuezhu Huang, Juveria Zaheer, Paul S. Links
Journal: American Journal of Psychiatry (2011)

A brief educational program for 10,000 rural physicians in China introduced them to psychiatric knowledge and skills, emphasizing suicide risk assessment and management. Six months after the program, the physicians reported positive changes in their attitudes toward psychiatry, applicability of their new knowledge, and more communication with specialists.
CD8+ T cells are recruited early to allergen exposure sites in atopy patch test reactions in human atopic dermatitis
Authors: Ana Hennino, Catherine Jean-Decoster, Françoise Giordano-Labadie, Sabine Debeer, Béatrice Vanbervliet, Aurore Rozières, Anne-Marie Schmitt, Jean-François Nicolas
Journal: Journal of Allergy and Clinical Immunology (2011)
The Role of Laparoscopic and Robotic Cystectomy in the Management of Muscle-Invasive Bladder Cancer With Special Emphasis on Cancer Control and Complications
Authors: Ben J. Challacombe, Bernard H. Bochner, Prokar Dasgupta, Inderbir Gill, Khurshid Guru, Harry Herr, Alexander Mottrie, Raj Pruthi, Joan Palou Redorta, Peter Wiklund
Journal: European Urology (2011)
Dephosphorylation and Intracellular Redistribution of Ventricular Connexin43 During Electrical Uncoupling Induced by Ischemia
Authors: Michael A. Beardslee, Deborah L. Lerner, Peter N. Tadros, James G. Laing, Eric C. Beyer, Kathryn A. Yamada, André G. Kléber, Richard B. Schuessler, Jeffrey E. Saffitz
Journal: Circulation Research (2000)

Electrical uncoupling at gap junctions during acute myocardial ischemia contributes to conduction abnormalities and reentrant arrhythmias. Increased levels of intracellular Ca(2+) and H(+) and accumulation of amphipathic lipid metabolites during ischemia promote uncoupling, but other mechanisms may play a role. We tested the hypothesis that uncoupling induced by acute ischemia is associated with changes in phosphorylation of the major cardiac gap junction protein, connexin43 (Cx43). Adult rat hearts perfused on a Langendorff apparatus were subjected to ischemia or ischemia/reperfusion. Changes in coupling were monitored by measuring whole-tissue resistance. Changes in the amount and distribution of phosphorylated and nonphosphorylated isoforms of Cx43 were measured by immunoblotting and confocal immunofluorescence microscopy using isoform-specific antibodies. In control hearts, virtually all Cx43 identified immunohistochemically at apparent intercellular junctions was phosphorylated. During ischemia, however, Cx43 underwent progressive dephosphorylation with a time course similar to that of electrical uncoupling. The total amount of Cx43 did not change, but progressive reduction in total Cx43 immunofluorescent signal and concomitant accumulation of nonphosphorylated Cx43 signal occurred at sites of intercellular junctions. Functional recovery during reperfusion was associated with increased levels of phosphorylated Cx43. These observations suggest that uncoupling induced by ischemia is associated with dephosphorylation of Cx43, accumulation of nonphosphorylated Cx43 within gap junctions, and translocation of Cx43 from gap junctions into intracellular pools.
Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study
Authors: R.K.C. Ngan, H.H.Y. Yiu, W.H. Lau, S. Yau, F.Y. Cheung, T.M. Chan, C.H. Kwok, C.Y. Chiu, S.K. Au, W. Foo, C.K. Law, K.C. Tse
Journal: Annals of Oncology (2002)
APOε4 is associated with enhanced in vivo innate immune responses in human subjects
Authors: Stephen C. Gale, Li Gao, Carmen Mikacenic, Susette M. Coyle, Nicholas Rafaels, Tanda Murray Dudenkov, Jennifer H. Madenspacher, David W. Draper, William Ge, Jim J. Aloor, Kathleen M. Azzam, Lihua Lai, Perry J. Blackshear, Steven E. Calvano, Kathleen C. Barnes, Stephen F. Lowry, Siobhan Corbett, Mark M. Wurfel, Michael B. Fessler
Journal: Journal of Allergy and Clinical Immunology (2014)
Randomized Trial of Quality Improvement Intervention to Improve Diabetes Care in Primary Care Settings
Authors: Patrick J. O’Connor, Jay Desai, Leif I. Solberg, Laurel A. Reger, A. Lauren Crain, Stephen E. Asche, Teresa L. Pearson, Cynthia K. Clark, William A. Rush, Linda M. Cherney, JoAnn M. Sperl-Hillen, Donald B. Bishop
Journal: Diabetes Care (2005)

OBJECTIVE—To assess the impact of a quality improvement (QI) intervention on the quality of diabetes care at primary care clinics. RESEARCH DESIGN AND METHODS—Twelve primary care medical practices were matched by size and location and randomized to intervention or control conditions. Intervention clinic staff were trained in a seven-step QI change process to improve diabetes care. Surveys and medical record reviews of 754 patients, surveys of 329 clinic staff, interviews with clinic leaders, and analysis of training session videotapes evaluated compliance with and impact of the intervention. Mixed-model nested analyses compared differences in the quality of diabetes care before and after intervention. RESULTS—All intervention clinics completed at least six steps of the seven-step QI change process in an 18-month period and, compared with control clinics, had broader staff participation in QI activities (P = 0.04), used patient registries more often (P = 0.03), and had better test rates for HbA1c (A1C), LDL, and blood pressure (P = 0.02). Other processes of diabetes care were unchanged. The intervention did not improve A1C (P = 0.54), LDL (P = 0.46), or blood pressure (P = 0.69) levels or a composite of these outcomes (P = 0.35). CONCLUSIONS—This QI change process was successfully implemented but failed to improve A1C, LDL, or blood pressure levels. Data suggest that to be successful, such a QI change process should direct more attention to specific clinical actions, such as drug intensification and patient activation.
Human hepatocyte growth factor levels in patients undergoing thoracic operations
Authors: E. Dikmen, M. Kara, U. Kisa, C. Atinkaya, S. Han, U. Sakinci
Journal: European Respiratory Journal (2005)

Human hepatocyte growth factor (hHGF) is the most potent mitogen identified for alveolar type II cells, and may have other important functions in the repair of the alveolar epithelium and compensatory lung growth. A study was conducted to evaluate the changes of serum hHGF levels in patients who underwent thoracic surgical procedures. The patients comprised 17 males and 14 females with a mean age of 47.1±13.5 yrs, who underwent either lung resection (LR group) or nonlung resection (nonLR group) thoracic procedures. The changes of hHGF levels were analysed in the pre- and post-operative periods in both groups. The pre-operative hHGF levels did not differ between the LR and the nonLR groups, which were 333.2±72.9 pg·mL −1 and 343.6±125.3 pg·mL −1 , respectively. The hHGF levels in the LR group significantly increased up to 433.6±128.1 pg·mL −1 and 430.8±128.2 pg·mL −1 in post-operative days 1 and 3, respectively. However, the same levels in the nonLR group appeared as 333.2±77.0 pg·mL −1 and 311.9±73.0 pg·mL −1 , respectively. In conclusion, the increases of serum human hepatocyte growth factor levels following pulmonary resection may imply the important role of human hepatocyte growth factor in lung regeneration or compensatory lung growth in humans.