tbuckley/cabot-search huggingface dataset:
Vaccination Strategy Determines the Emergence and Dominance of CD8+ T-Cell Epitopes in a FVB/N Rat HER-2/<i>neu</i>Mouse Model of Breast Cancer
Authors: Reshma Singh, Yvonne Paterson
Journal: Cancer Research (2006)

Abstract The HER-2/neu oncogene has &amp;gt;25 HLA epitopes, yet only one FVB/N mouse CD8+ T-cell epitope has been mapped to date. This epitope has been termed the immunodominant epitope for the FVB/N mouse, but we propose that the vaccination strategy determines the dominance of epitopes. Using a series of overlapping peptides, we have mapped another CD8+ T-cell epitope that emerges in the FVB/N mouse following vaccination with Listeria monocytogenes–based vaccines that express fragments of HER-2/neu. Following the identification of this novel H-2Kq-restricted epitope, we sought to compare the T-cell response to this epitope with the previously identified PDSLRDLSVF epitope. This newly identified epitope and the previously identified epitope lie within fragments contained in different vaccines, the PDSLRDLSVF epitope in Lm-LLO-EC2 and the newly identified PYNYLSTEV epitope in Lm-LLO-EC1; thus, it has been possible to compare the responses of these epitopes independent of any competing response between the epitopes. CTL analysis of individual peptide-pulsed target cells and intracellular cytokine stain for IFN-γ produced by splenocytes from Lm-LLO-EC1 compared with Lm-LLO-EC2 vaccinated FVB/N mice shows that there is no difference between the responses generated to either of these epitopes. We also show that the avidity of the CD8+ T cells for either of these epitopes is similar based on the concentration of peptide necessary to mediate similar levels of lysis of target cells. In addition, HER-2/neu DNA vaccination followed by CTL analysis further showed that both of these peptides can emerge as epitopes. (Cancer Res 2006; 66(15): 7748-57)
Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus
Authors: Noritaka Oyama, Ien Chan, Sallie M. Neill, Andrew P. South, Fenella Wojnarowska, Yoshio Kawakami, David D’Cruz, Kirti Mepani, Graham J. Hughes, Balbir S. Bhogal, Fumio Kaneko, Martin M. Black, John A. McGrath
Journal: Journal of Clinical Investigation (2004)

Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients' sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus.
Novel Lipid Mediators Promote Resolution of Acute Inflammation
Authors: Matthew Spite, Charles N. Serhan
Journal: Circulation Research (2010)

The resolution of acute inflammation is a process that allows for inflamed tissues to return to homeostasis. Resolution was held to be a passive process, a concept now overturned with new evidence demonstrating that resolution is actively orchestrated by distinct cellular events and endogenous chemical mediators. Among these, lipid mediators, such as the lipoxins, resolvins, protectins, and newly identified maresins, have emerged as a novel genus of potent and stereoselective players that counter-regulate excessive acute inflammation and stimulate molecular and cellular events that define resolution. Given that uncontrolled, chronic inflammation is associated with many cardiovascular pathologies, an appreciation of the endogenous pathways and mediators that control timely resolution can open new terrain for therapeutic approaches targeted at stimulating resolution of local inflammation, as well as correcting the impact of chronic inflammation in cardiovascular disorders. Here, we overview and update the biosynthesis and actions of proresolving lipid mediators, highlighting their diverse protective roles relevant to vascular systems and their relation to aspirin and statin therapies.
Overexpression of the Colony-Stimulating Factor (CSF-1) and/or Its Receptor <b> <i>c-fms</i> </b> in Mammary Glands of Transgenic Mice Results in Hyperplasia and Tumor Formation
Authors: Nameer Kirma, Roopa Luthra, Jeremy Jones, Ya-Guang Liu, Hareesh B. Nair, Usha Mandava, Rajeshwar Rao Tekmal
Journal: Cancer Research (2004)

A number of recent studies have suggested that the colony-stimulating factor (CSF-1) and its receptor c-fms may be involved in the development of mammary glands during lactation and breast cancer. To study the role of CSF-1 or its receptor in initiation of mammary tumorigenesis, we have generated two independent lines of transgenic mice that overexpress either CSF-1 or c-fms under the control of the mouse mammary tumor virus promoter. Mammary glands of the virgin CSF-1 transgenic mice show increased ductal branching, hyperplasia, dysplasia, and other preneoplastic changes, which are indicative of increased cellular proliferation. Similar changes were also evident in the mammary glands of the c-fms transgenic mice. These changes became more prominent with age and resulted in mammary tumor formation. Moreover, secondary events like dimethylbenz(a)anthracene treatment accelerated mammary tumor formation in these mice. Although the expression of estrogen receptor alpha was not significantly changed in either of the transgenic mouse strains, progesterone receptor levels was higher in both transgenic lines as compared with the nontransgenic littermates. Expression of G1 cyclins was prominently increased in the mammary glands of both the CSF-1 and c-fms transgenic lines, suggesting increased cell cycle progression in these strains. In addition, the proliferation marker proliferating cell nuclear antigen (PCNA) and the mitogen-responsive transcription factor c-jun were also increased as compared with the nontransgenic controls. These findings, along with the histological data, support the hypothesis that CSF-1 and its receptor are involved in the etiology of breast cancer.
Biomarker Changes During Neoadjuvant Anastrozole, Tamoxifen, or the Combination: Influence of Hormonal Status and HER-2 in Breast Cancer—A Study from the IMPACT Trialists
Authors: Mitch Dowsett, Steve R. Ebbs, J. Michael Dixon, Anthony Skene, Clive Griffith, Irene Boeddinghaus, Janine Salter, Simone Detre, Margaret Hills, Susan Ashley, Stephen Francis, Geraldine Walsh, Ian E. Smith
Journal: Journal of Clinical Oncology (2005)

To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy.The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment.52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks.These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.
RABBIT HOMOCYTOTROPIC ANTIBODY
Authors: Nathan J. Zvaifler, Jennifer O. Robinson
Journal: The Journal of Experimental Medicine (1969)

Rabbits immunized with egg albumin produce a homocytotropic antibody. The antibody is identified by its ability to produce passive anaphylaxis in rabbit skin. The time of appearance of this antibody, its persistence and recall after booster injections depends, in part, on the route of immunization and the adjuvant employed. The physicochemical characteristics of the homocytotropic antibody obtained was similar regardless of the immunization schedule used. The anaphylactic activity of these antisera showed some heterogeneity when chromatographed on diethylaminoethyl (DEAE)-cellulose, but all fractions were inactivated by heating and absorption with a specific antisera. The anaphylactic activity could be separated from rabbit IgG and IgA, and was not blocked by absorption with antisera specific for these classes of immunoglobulins. Anaphylactic activity was completely removed by absorption with a specific antiserum which did not react with any of the known rabbit immunoglobulins. The passive cutaneous anaphylaxis titer of a rabbit serum containing homocytotropic antibody was reduced by 50% after absorption with an antisera (anti-FcND) specific for human IgE. On the basis of these distinctive physicochemical characteristics, it is concluded that rabbit homocytotropic antibody represents a unique class of rabbit immunoglobulin, analogous to human IgE.
Consolidation Radiotherapy in Patients With Advanced Hodgkin's Lymphoma: Survival Data From the UKLG LY09 Randomized Controlled Trial (ISRCTN97144519)
Authors: Peter W.M. Johnson, Matthew R. Sydes, Barry W. Hancock, Michael Cullen, John A. Radford, Sally P. Stenning
Journal: Journal of Clinical Oncology (2010)

This study analyzed the outcomes of nonrandomized consolidation radiotherapy (RT) given after chemotherapy in the initial treatment of advanced Hodgkin's lymphoma (HL). The results were collected prospectively within a randomized controlled trial of induction chemotherapy.Patients were randomly assigned between doxorubicin, bleomycin, vinblastine, and dacarbazine and one of two prespecified multidrug regimens. At least six cycles of chemotherapy were planned, with up to eight for patients showing slower response. Involved-field RT was recommended for incomplete response to chemotherapy or bulk disease at presentation. The primary outcome measure was progression-free survival (PFS), landmarked from the end of chemotherapy.Among 807 patients randomly assigned, 702 achieved objective response. Postchemotherapy RT for consolidation was reported in 300 (43%). With median follow-up of 6.9 years, 161 PFS events and 83 deaths were reported. Baseline characteristics showed more patients with bulk disease having RT (190 [63%] v 111 [28%]) and only partial response after chemotherapy (150 [50%] v 36 [9%]). Other baseline characteristics were similar. PFS was superior for patients having RT (hazard ratio [HR], 0.43; 95% CI, 0.30 to 0.60) with 5-year PFS 71% without RT, 86% with RT. A similar advantage was seen for overall survival (HR, 0.47; 95% CI, 0.29 to 0.77). There was no evidence of heterogeneity of treatment effect across subgroups.Patients who received consolidation RT apparently had better outcomes, consistently across all prognostic groups which persisted in multivariate analysis. This suggests that RT contributes significantly to the cure rate for advanced HL, although patient selection for combined modality treatment requires better definition in prospective trials.
Effects of Abciximab on the Architecture of Platelet-Rich Clots in Patients With Acute Myocardial Infarction Undergoing Primary Coronary Intervention
Authors: J. P. Collet, G. Montalescot, C. Lesty, Z. Mishal, J. Soria, R. Choussat, G. Drobinski, C. Soria, P. Pinton, P. Barragan, D. Thomas
Journal: Circulation (2001)

Background —Abciximab plus aspirin improves the TIMI 3 flow rate of the infarct-related artery in patients treated with either percutaneous coronary intervention or thrombolysis. The present study investigated whether the reperfusion efficacy of abciximab relates to modifications of clot architecture in patients admitted for acute myocardial infarction (AMI). Methods and Results —A total of 23 AMI patients in the Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long term follow-up (ADMIRAL) trial received, in a double-blind fashion, either abciximab (n=13) or placebo (n=10) before primary stenting. Viscoelastic (G′ in dyne/cm 2 ) and morphological (mean platelet aggregate surface area [SAG] in μm 2 ) indexes of ex vivo platelet-rich clots (PRC) were assessed in a double-blind fashion before and after the bolus administration of abciximab or placebo. G′ and SAG reflect the mechanical and morphological impact of activated platelets on the PRC fibrin network, respectively. Abciximab administration reduced G′ by 63% ( P =0.0001) and SAG by 65% ( P =0.0007), and no effect was seen in the placebo group. These abciximab-related changes increased fibrin exposure as a consequence of the platelet-aggregate surface reduction and may have improved endogenous fibrinolysis. These effects were identified in all patients, independent of previous heparin administration. Conclusions —Abciximab dramatically reduces platelet aggregate size and increases the fibrin accessibility of ex vivo PRC in AMI patients. These modifications could participate in the better coronary artery patency observed with abciximab.
Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study
Authors: Xuya Huang, Bharath Kumar Cheripelli, Suzanne M Lloyd, Dheeraj Kalladka, Fiona Catherine Moreton, Aslam Siddiqui, Ian Ford, Keith W Muir
Journal: The Lancet Neurology (2015)
Neuron-Glial Interactions in Blood-Brain Barrier Formation
Authors: Swati Banerjee, Manzoor A. Bhat
Journal: Annual Review of Neuroscience (2007)

The blood brain barrier (BBB) evolved to preserve the microenvironment of the highly excitable neuronal cells to allow for action potential generation and propagation. Intricate molecular interactions between two main cell types, the neurons and the glial cells, form the underlying basis of the critical functioning of the nervous system across species. In invertebrates, interactions between neurons and glial cells are central in establishing a functional BBB. However, in vertebrates, the BBB formation and function is coordinated by interactions between neurons, glial cells, and endothelial cells. Here we review the neuron-glial interaction-based blood barriers in invertebrates and vertebrates and provide an evolutionary perspective as to how a glial-barrier system in invertebrates evolved into an endothelial barrier system. We also summarize the clinical relevance of the BBB as this protective barrier becomes disadvantageous in the pharmacological treatment of various neurological disorders.
Hypertension
Authors: Luuk te Riet, Joep H.M. van Esch, Anton J.M. Roks, Anton H. van den Meiracker, A.H. Jan Danser
Journal: Circulation Research (2015)

Blockers of the renin-angiotensin-aldosterone system (RAAS), that is, renin inhibitors, angiotensin (Ang)-converting enzyme (ACE) inhibitors, Ang II type 1 receptor antagonists, and mineralocorticoid receptor antagonists, are a cornerstone in the treatment of hypertension. How exactly they exert their effect, in particular in patients with low circulating RAAS activity, also taking into consideration the so-called Ang II/aldosterone escape that often occurs after initial blockade, is still incompletely understood. Multiple studies have tried to find parameters that predict the response to RAAS blockade, allowing a personalized treatment approach. Consequently, the question should now be answered on what basis (eg, sex, ethnicity, age, salt intake, baseline renin, ACE or aldosterone, and genetic variance) a RAAS blocker can be chosen to treat an individual patient. Are all blockers equal? Does optimal blockade imply maximum RAAS blockade, for example, by combining ≥2 RAAS blockers or by simply increasing the dose of 1 blocker? Exciting recent investigations reveal a range of unanticipated extrarenal effects of aldosterone, as well as a detailed insight in the genetic causes of primary aldosteronism, and mineralocorticoid receptor blockers have now become an important treatment option for resistant hypertension. Finally, apart from the deleterious ACE-Ang II-Ang II type 1 receptor arm, animal studies support the existence of protective aminopeptidase A-Ang III-Ang II type 2 receptor and ACE2-Ang-(1 to 7)-Mas receptor arms, paving the way for multiple new treatment options. This review provides an update about all these aspects, critically discussing the many controversies and allowing the reader to obtain a full understanding of what we currently know about RAAS alterations in hypertension.
Dependency of Pial Arterial and Arteriolar Diameter on Perivascular Osmolarity in the Cat
Authors: M. WAHL, W. KUSCHINSKY, O. BOSSE, K. THURAU
Journal: Circulation Research (1973)

The effect of perivascular osmolarity on the diameter of pial arteries was studied in cats by the microapplication technique. Between 251 and 360 mosmoles/liter, concentration-response curves were obtained for single vessels. Constriction occurred when perivascular osmolarity was decreased below 317 mosmoles/liter, and dilation occurred at osmolarities above this value. The effect was the same whether the osmolarity was changed by addition of mannitol or NaCl. Reduction of sodium concentration from 156 to 133 mEq/liter at constant osmolarity did not affect arteriolar diameter, but greater reductions in sodium concentration induced vasoconstriction. The results indicate that the resistance of pial arteries can be influenced by local changes in perivascular osmolarity.
Comorbidity at COPD - is actual problem of pulmonology
Authors: Yuriy Mostovoy, Tetyana Konstantynovych, Lesya Rasputina, Mariia Ovcharuk, Alina Dovgan
Journal: European Respiratory Journal (2014)

Management of COPD patients with concomitant diseases is a difficult problem of modern medicine. This applies to combination of COPD with essential hypertension (EH) , diabetes mellitus (DM), psychosomatic disorders (PD) and others. According to our data, based on statistical analysis of 15134 case history tendency of growing a combination of EH and COPD currently in 13 % of COPD patients diagnosed hypertension. In these patients a number of cardiorespiratory indexes significantly worse than similar for isolated course of COPD and EH. This includes parameters FEV1 and FEV1/FVC, index of blood pressure time, heart rate, intensity of endothelial dysfunction. The comorbidity of COPD and DM in hospitalized patients during last years was 9.1%. The diagnosis of DM is established in the hospital. In COPD patients with concomitant DM were significantly more likely than those with isolated these diseases arose community acquired pneumonia required hospitalization and repeated courses of antibiotic therapy. Anxiety and depression are major comorbidities in COPD that significantly worse prognosis. High levels of neurotism in COPD patients diagnosed in 79.3% (vs 14.3 % among healthy control group), a high level of reactive anxiety in COPD patients – in 41.8 % (vs 23,8 % of control), depression in COPD patients - in 23.2 % (vs 4.7% of control). A number of clinical and functional parameters in patients with COPD associated with PD were significantly worse than in COPD patients without PD. The problem of comorbidity of COPD becomes more actual for use of drugs for basic treatment and for treat of comorbidities should be carefully crafted with regard to occurrence of both positive and negative effects.
Psychiatric Disorders in Rescue Workers After the Oklahoma City Bombing
Authors: Carol S. North, Laura Tivis, J. Curtis McMillen, Betty Pfefferbaum, Edward L. Spitznagel, Jann Cox, Sara Nixon, Kenneth P. Bunch, Elizabeth M. Smith
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Psychiatric disorders were studied in a volunteer group of 181 firefighters who served as rescue/recovery workers after the Oklahoma City bombing. METHOD: Approximately 34 months after the disaster, the authors retrospectively assessed psychopathology both before and after the bombing with the Diagnostic Interview Schedule. Findings for male rescue workers were compared with those of male primary victims who had been in the direct path of the blast and who had been assessed with the same instrument. RESULTS: The prevalence of posttraumatic stress disorder related to the bombing was significantly lower in male rescue workers (13%) than in male primary victims (23%). High rates of alcohol disorders (postdisaster: 24%; lifetime: 47%) were seen among all rescue workers, with virtually no new cases occurring after the bombing. CONCLUSIONS: The resilience seen in firefighters may be related to their career selection, their preparedness and experience, the fewer injuries they suffered, and postdisaster mental health interventions. However, alcohol disorders were endemic before the disaster, indicating a need for ongoing programs targeting this problem.
Immune responsiveness in renal transplant recipients: Mycophenolic acid severely depresses humoral immunity in vivo
Authors: Rob J. Rentenaar, Frank N.J. Van Diepen, René T. Meijer, Sugianto Surachno, Joep M. Wilmink, Peter Th. A. Schellekens, Steven T. Pals, René A.W. Van Lier, Ineke J.M. Ten Berge
Journal: Kidney International (2002)
Successful Treatment of Leptomeningeal Disease in Colorectal Cancer With a Regimen of Bevacizumab, Temozolomide, and Irinotecan
Authors: Geoffrey Y. Ku, George Krol, David H. Ilson
Journal: Journal of Clinical Oncology (2007)

A B Fig 1. Magnetic resonance imaging of the spine (A) after one cycle of treatment and (B) follow-up study 3 months later after four treatment cycles.Sagittal T1-weighted sequences reveal almost complete resolution of linear and nodular enhancement around the (arrows) conus medullaris and roots of cauda equina.
Emergence of tigecycline-resistant Klebsiella pneumoniae after tigecycline therapy for complicated urinary tract infection caused by carbapenem-resistant Escherichia coli
Authors: Hsih-Yeh Tsai, Chun-Hsing Liao, Aristine Cheng, Chia-Ying Liu, Yu-Tsung Huang, Wang-Huei Sheng, Po-Ren Hsueh
Journal: Journal of Infection (2012)