tbuckley/cabot-search huggingface dataset:
Electrophysiological Mechanisms and Determinants of Vagal Maneuvers for Termination of Paroxysmal Supraventricular Tachycardia
Authors: Zu-Chi Wen, Shih-Ann Chen, Ching-Tai Tai, Chern-En Chiang, Chuen-Wang Chiou, Mau-Song Chang
Journal: Circulation (1998)

Background —The vagal maneuvers used for termination of paroxysmal supraventricular reentrant tachycardia (PSVT) appear to involve more complex mechanisms than we have known, and further study should be done to explore the possible mechanisms. Methods and Results —In this study, 133 patients with PSVT and 30 age- and sex-matched control subjects were included. We assessed the effects of different vagal maneuvers on termination of PSVT and compared baroreflex sensitivity and β-adrenergic sensitivity between the patients with PSVT and control subjects. Out of 85 patients with atrioventricular reciprocating tachycardia (AVRT), vagal maneuvers terminated in 45 (53%). Of these, 28 (33%) terminated in the antegrade limb and 17 (20%) terminated in the retrograde limb. Out of 48 patients with atrioventricular nodal reentrant tachycardia (AVNRT), vagal maneuvers terminated the tachycardia in the antegrade slow pathway (14%) or in the retrograde fast pathway (19%). Baroreflex sensitivity was poorer but isoproterenol sensitivity test better in patients with AVNRT. Poorer antegrade atrioventricular node conduction properties and better vagal response determined successful antegrade termination of AVRT by vagal maneuvers. Poorer retrograde accessory pathway conduction property but better vagal response determined successful retrograde termination of AVRT. Better sympathetic and vagal response associated with poorer retrograde atrioventricular node conduction determined retrograde termination of AVNRT by the Valsalva maneuver. Conclusions —Both the vagal response and conduction properties of the reentrant circuit determine the tachycardia termination by vagal maneuvers. Improved understanding of the interaction of autonomic and electrophysiological mechanisms in maintaining or terminating PSVT may provide important insight into the pathophysiology of these two tachycardias.
The dorsal medial prefrontal (anterior cingulate) cortex–amygdala aversive amplification circuit in unmedicated generalised and social anxiety disorders: an observational study
Authors: Oliver J Robinson, Marissa Krimsky, Lynne Lieberman, Phillip Allen, Katherine Vytal, Christian Grillon
Journal: The Lancet Psychiatry (2014)

We have delineated, across four prior studies, the role of positive dorsal medial prefrontal/anterior cingulate cortex (dmPFC/ACC)-amygdala circuit coupling during aversive processing in healthy individuals under stress. This translational circuit, termed the 'aversive amplification circuit', is thought to drive adaptive, harm-avoidant behavior in threatening environments. Here, in a natural progression of this prior work, we confirm that this circuit also plays a role in the pathological manifestation of anxiety disorders.Forty-five unmedicated participants (N=22 generalized and social anxiety disorder/N=23 controls) recruited from Washington DC metropolitan area completed a simple emotion identification task during functional magnetic resonance imaging at the National Institutes of Health, Bethesda, MD, USA.As predicted, a diagnosis by valence interaction was seen in whole-brain amygdala connectivity within the dmPFC/ACC clusters identified in our prior study; driven by significantly greater circuit coupling during fearful versus happy face processing in anxious, but not healthy, participants. Critically, and in accordance with contemporary theoretical approaches to psychiatry, circuit coupling correlated positively with self-reported anxious symptoms, providing evidence of a continuous circuit-subjective symptomatology relationship.We track the functional role of a single neural circuit from its involvement in adaptive threat-biases under stress, to its chronic engagement in anxiety disorders in the absence of experimentally induced stress. Thus, we uniquely map a mood and anxiety related circuit across its adaptive and maladaptive stages. Clinically, this may provide a step towards a more mechanistic spectrum-based approach to anxiety disorder diagnosis and may ultimately lead to more targeted treatments.
Quantification of Excision Repair Cross-Complementing Group 1 and Survival in p16-Negative Squamous Cell Head and Neck Cancers
Authors: Ranee Mehra, Fang Zhu, Dong-Hua Yang, Kathy Q. Cai, JoEllen Weaver, Mahendra K. Singh, Anna S. Nikonova, Erica A. Golemis, Douglas B. Flieder, Harry S. Cooper, Miriam Lango, John A. Ridge, Barbara Burtness
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Multimodality treatment of squamous cell carcinoma of the head and neck (SCCHN) often involves radiotherapy and cisplatin-based therapy. Elevated activity of DNA repair mechanisms, such as the nucleotide excision repair (NER) pathway, of which ERCC1 is a rate-limiting element, are associated with cisplatin and possibly RT resistance. We have determined excision repair cross-complementing group 1 (ERCC1) expression in human papillomavirus (HPV)-negative SCCHN treated with surgery [±adjuvant radiotherapy/chemoradiation (CRT)]. Experimental Design: We assessed ERCC1 protein expression in archival tumors using immunofluorescence staining and automatic quantitative analysis (AQUA) with three antibodies to ERCC1 (8F1, FL297, and HPA029773). Analysis with Classification and Regression Tree (CART) methods ascertained the cutoff points between high/low ERCC1 expression. Multivariable analysis adjusted for age, T, and N stage. Kaplan–Meier curves determined median survival. ERCC1 expression at initial tumor presentation and in recurrent disease were compared. Performance characteristics of antibodies were assessed. Results: ERCC1 low/high groups were defined on the basis of AQUA analysis with 8F1/2009, FL297, and HPA029773. Among patients treated with surgery plus adjuvant radiotherapy/CRT, longer median survival was observed in ERCC1-low versus ERCC1-high tumors (64 vs. 29 months; P = 0.02; HPA029773). Data obtained with HPA029773 indicated no survival difference among patients treated only with surgery. Recurrent cancers had lower ERCC1 AQUA scores than tumors from initial presentation. Extensive characterization indicated optimal specificity and performance by the HPA029773 antibody. Conclusions: Using AQUA, with the specific ERCC1 antibody HPA029773, we found a statistical difference in survival among high/low-ERCC1 tumors from patients treated with surgery and adjuvant radiotherapy. Clin Cancer Res; 19(23); 6633–43. ©2013 AACR.
Hepatocyte growth factor receptor and the c-Met oncogene
Authors: Nelson Fausto
Journal: Hepatology (1991)

Hepatocyte growth factor (HGF) is a plasminogen-like protein thought to be a humoral mediator of liver regeneration. A 145-kilodalton tyrosyl phosphoprotein observed in rapid response to HGF treatment of intact target cells was identified by immunoblot analysis as the β subunit of the c- met proto-oncogene product, a membrane-spanning tyrosine kinase. Covalent cross-linking of 125 I-labeled ligand to cellular proteins of appropriate size that were recognized by antibodies to c- met directly established the c- met product as the cell-surface receptor for HGF.
The Aryl Propionic Acid<i>R</i>-Flurbiprofen Selectively Induces p75NTR-Dependent Decreased Survival of Prostate Tumor Cells
Authors: Emily J. Quann, Fatima Khwaja, Kenton H. Zavitz, Daniel Djakiew
Journal: Cancer Research (2007)

Abstract Epidemiologic studies show that patients chronically consuming nonsteroidal anti-inflammatory drugs (NSAID) for arthritis exhibit a reduced incidence of prostate cancer. In addition, some NSAIDs show anticancer activity in vitro. NSAIDs exert their anti-inflammatory effects by inhibiting cyclooxygenase (COX) activity; however, evidence suggests that COX-independent mechanisms mediate decreased prostate cancer cell survival. Hence, we examined the effect of selected aryl propionic acid NSAIDs and structurally related compounds on the decreased survival of prostate cancer cell lines PC-3, DU-145, and LNCaP by induction of the p75NTR protein. p75NTR has been shown to function as a tumor suppressor in the prostate by virtue of its intracellular death domain that can initiate apoptosis and inhibit growth. The most efficacious compounds for induction of p75NTR and decreased survival, in rank-order, were R-flurbiprofen, ibuprofen, oxaprozin, fenoprofen, naproxen, and ketoprofen. Because R-flurbiprofen and ibuprofen exhibited the greatest efficacy, we examined their dose-dependent specificity of induction for p75NTR relative to other members of the death receptor family. Whereas treatment with R-flurbiprofen or ibuprofen resulted in a massive induction of p75NTR protein levels, the expression of Fas, p55TNFR, DR3, DR4, DR5, and DR6 remained largely unchanged. Moreover, transfection of either cell line before R-flurbiprofen or ibuprofen treatment with a dominant negative form of p75NTR to antagonize p75NTR activity or p75NTR small interfering RNA to prevent p75NTR protein expression rescued both cell lines from decreased survival. Hence, R-flurbiprofen and ibuprofen selectively induce p75NTR-dependent decreased survival of prostate cancer cells independently of COX inhibition. [Cancer Res 2007;67(7):3254–62]
Effect of Depression on Diagnosis, Treatment, and Mortality of Men With Clinically Localized Prostate Cancer
Authors: Sandip M. Prasad, Scott E. Eggener, Stuart R. Lipsitz, Michael R. Irwin, Patricia A. Ganz, Jim C. Hu
Journal: Journal of Clinical Oncology (2014)

Purpose Although demographic, clinicopathologic, and socioeconomic differences may affect treatment and outcomes of prostate cancer, the effect of mental health disorders remains unclear. We assessed the effect of previously diagnosed depression on outcomes of men with newly diagnosed prostate cancer. Patients and Methods We performed a population-based observational cohort study using Surveillance, Epidemiology, and End Results-Medicare linked data of 41,275 men diagnosed with clinically localized prostate cancer from 2004 to 2007. We identified 1,894 men with a depressive disorder in the 2 years before the prostate cancer diagnosis and determined its effect on treatment and survival. Results Men with depressive disorder were older, white or Hispanic, unmarried, resided in nonmetropolitan areas and areas of lower median income, and had more comorbidities (P &lt; .05 for all), but there was no variation in clinicopathologic characteristics. In adjusted analyses, men with depressive disorder were more likely to undergo expectant management for low-, intermediate-, and high-risk disease (P ≤ .05, respectively). Conversely, depressed men were less likely to undergo definitive therapy (surgery or radiation) across all risk strata (P &lt; .01, respectively). Depressed men experienced worse overall mortality across risk strata (low: relative risk [RR], 1.86; 95% CI, 1.48 to 2.33; P &lt; .001; intermediate: RR, 1.25; 95% CI, 1.06 to 1.49; P = .01; high: RR, 1.16; 95% CI, 1.03 to 1.32; P = .02). Conclusion Men with intermediate- or high-risk prostate cancer and a recent diagnosis of depression are less likely to undergo definitive treatment and experience worse overall survival. The effect of depression disorders on prostate cancer treatment and survivorship warrants further study, because both conditions are relatively common in men in the United States.
Mapping common deleted regions on 5p15 in cervical carcinoma and their occurrence in precancerous lesions.
Authors: Hugo Arias-Pulido, Gopeshwar Narayan, Hernan Vargas, Mahesh Mansukhani, Vundavalli VVS Murty
Journal: Molecular Cancer (2002)

Previous studies have shown that the short arm of chromosome 5 (5p) exhibit frequent genetic changes in invasive cervical carcinoma (CC), and that these changes arise early during the carcinogenesis, in precancerous lesions. These data therefore suggest that loss of candidate tumor suppressor genes located on 5p is associated with the development of CC. However, the precise location of 5p deletions is not known. We performed a detailed deletion mapping of 5p in 60 cases of invasive CC. We found that 60% of the tumors exhibit a 5p loss of heterozygosity (LOH). The patterns of LOH allowed us to identify two minimal regions of deletions, one at 5p15.3 spanning a 5.5 cM genetic distance and a second site of 7 cM at 5p15.2-15.3. In addition, we also identified 5p deletions in 16% lesions of high-grade cervical intraepithelial neoplasia (CIN). 5p LOH was found in 63% of HPV 16 positive tumors, while only 33% tumors with other HPV-types had 5p LOH. The differences in frequency of 5p LOH between tumors harboring HPV16 in combination with other HPV types and tumors harboring HPV16 DNA alone were significantly higher, suggesting a synergistic effect of high-risk types in causing genomic instability. These findings implicate the presence of tumor suppressor gene(s) on 5p relevant to CC tumorigenesis.
TCT-630 Impact of Calcified Plaque on Stent Strut Distribution of Bioresorbable Vascular Scaffolds Versus Metallic Everolimus-eluting Stents: An Optical Coherence Tomography Analysis
Authors: Katsumasa Sato, Azeem Latib, Vasileios F. Panoulas, Hiroyoshi Kawamoto, Tadashi Miyazaki, Toru Naganuma, Antonio Colombo
Journal: Journal of the American College of Cardiology (2014)
How Well Do Physicians Use Electronic Information Retrieval Systems?
Authors: William R. Hersh, David H. Hickam
Journal: JAMA (1998)

Despite the proliferation of electronic information retrieval (IR) systems for physicians, their effectiveness has not been well assessed. The purpose of this review is to provide a conceptual framework and to apply the results of previous studies to this framework.All sources of medical informatics and information science literature, including MEDLINE, along with bibliographies of textbooks in these areas, were searched from 1966 to January 1998.All articles presenting either classifications of evaluation studies or their results, with an emphasis on those studying use by physicians.A framework for evaluation was developed, consisting of frequency of use, purpose of use, user satisfaction, searching utility, search failure, and outcomes. All studies were then assessed based on the framework.Due to the heterogeneity and simplistic study designs, no meta-analysis of studies could be done. General conclusions were drawn from data where appropriate. A total of 47 articles were found to include an evaluation component and were used to develop the framework. Of these, 21 articles met the inclusion criteria for 1 or more of the categories in the framework. Most use of IR systems by physicians still occurs with bibliographic rather than full-text databases. Overall use of IR systems occurs just 0.3 to 9 times per physician per month, whereas physicians have 2 unanswered questions for every 3 patients.Studies comparing IR systems with different searching features have not shown that advanced searching methods are significantly more effective than simple text word methods. Most searches retrieve only one fourth to one half of the relevant articles on a given topic and, once retrieved, little is known about how these articles are interpreted or applied. These studies imply that further research and development are needed to improve system utility and performance.
Gut associated lymphoid tissue: a morphological and immunocytochemical study of the human appendix.
Authors: J Spencer, T Finn, P G Isaacson
Journal: Gut (1985)

Gut associated lymphoid tissue in 15 normal appendices has been characterised in tissue sections using both morphological criteria and immunocytochemical techniques. A panel of monoclonal and polyclonal antibodies was used including antibodies to B-cells, T-cells, macrophages, HLA DR and immunoglobulins. The lymphoid tissue in the appendix was shown to bear a strong resemblance to that in lymph nodes with the exception of the region where the appendix follicles associate with the dome epithelium, which has no lymph node equivalent. This zone of cells between the lymphoid follicles and the dome epithelium termed the 9mixed cell zone9 has been shown to contain an abundance of HLA DR-bearing cells, some of which have irregular nuclear morphology and resemble follicle centre cells. These cells were seen to extend into the epithelium of the dome but not the crypts. Using a monoclonal anti-B-cell antibody a population of B-cells was detected in the equivalent areas of mixed cell zone and epithelium and quantitative studies showed that these intraepithelial B-cells comprised approximately 4-5% of the cells in the epithelium. The mixed cell zone was also seen to contain T-cells, S-100 protein-containing macrophages and occasional lysozyme-containing macrophages. Plasma cells were rarely seen in this area.
Regulation of Cancer Stem Cells by Cytokine Networks: Attacking Cancer's Inflammatory Roots
Authors: Hasan Korkaya, Suling Liu, Max S. Wicha
Journal: Clinical Cancer Research (2011)

Abstract There is substantial evidence that many human cancers are driven by a subpopulation of cells that display stem cell properties. These cancer stem cells (CSC) may also contribute to metastasis and treatment resistance. Furthermore, just as normal stem cells are regulated by their microenvironment, or niche, CSCs interact with and in turn are regulated by cells in the tumor microenvironment. These interactions involve inflammatory cytokines, such as interleukin (IL)-1, IL-6, and IL-8, which in turn activate Stat3/NF-κB pathways in both tumor and stromal cells. Activation of these pathways stimulates further cytokine production, generating positive feedback loops that in turn drive CSC self-renewal. These cytokine loops and the pathways they regulate resemble those activated during chronic inflammation and wound healing, and may contribute to the known link between inflammation and cancer. Inhibitors of these cytokines and their receptors have been developed as anti-inflammatory agents. By blocking signals from the tumor microenvironment, these agents have the potential to target CSCs. Future clinical trials using these compounds will be needed to determine whether targeting the CSC population has clinical benefit. Clin Cancer Res; 17(19); 6125–9. ©2011 AACR.
Innate Immunity Influences Long-term Outcomes after Human Lung Transplant
Authors: Scott M. Palmer, Lauranell H. Burch, Anil J. Trindade, R. Duane Davis, Walter F. Herczyk, Nancy L. Reinsmoen, David A. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Lung transplantation is characterized by very high rates of acute and chronic allograft rejection. We hypothesize that activation of innate immunity augments adaptive immunity, leading to rejection after lung transplantation. In support of this idea, we have recently demonstrated that lung recipients heterozygous for either of two functional polymorphisms (Asp299Gly or Thr399Ile) in Toll-like receptor 4 (TLR4) associated with endotoxin hyporesponsiveness have decreased acute rejection over the first 6 months after transplant.In the current analysis, we sought to extend our initial observations and investigate the effect of these TLR4 polymorphisms on post-transplant acute rejection beyond the first 6 months, bacterial infections, bronchiolitis obliterans syndrome, and survival.Genotyping was performed on 170 lung transplant recipients.Recipients heterozygous for either Asp299Gly or Thr399Ile had significantly reduced frequency (p = 0.02) and incidence of acute rejection (p = 0.04) sustained over 3 years after transplant, but no differences were observed in the overall onset of bronchiolitis obliterans syndrome. A trend, however, toward reduced onset of bronchiolitis obliterans syndrome grade 2 or 3 was observed in TLR4 heterozygotes.Our results demonstrate that activation of recipient innate immune responses through TLR4 has a significant and sustained effect on the development of acute lung rejection. Targeting innate immune signaling represents a promising area for future clinical studies in the prevention of lung allograft rejection.
Hypoxia and Hypoxia-Inducible Factor-1 Target Genes in Central Nervous System Radiation Injury
Authors: Robert A. Nordal, Andras Nagy, Melania Pintilie, C. Shun Wong
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Microvascular permeability changes and loss of blood-brain barrier integrity are important features of central nervous system (CNS) radiation injury. Expression of vascular endothelial growth factor (VEGF), an important determinant of microvascular permeability, was examined to assess its role in CNS radiation damage. Because hypoxia mediates VEGF up-regulation through hypoxia-inducible factor-1α (HIF1α) induction, we studied the relationships of hypoxia, HIF1α expression, and expression of VEGF in this damage pathway. Experimental Design: Expression of HIF1α, VEGF, and another hypoxia-responsive gene, glucose transporter-1, was assessed in the irradiated rat spinal cord using immunohistochemistry and in situ hybridization. Hypoxic areas were identified using the nitroimidazole 2-(2-nitro-1H-imidazole-l-yl)-N-(2,2,3,3,3,-pentafluoropropyl) acetamide. To determine the causal importance of VEGF expression in radiation myelopathy, we studied the response of transgenic mice with greater (VEGF-Ahi/+), reduced (VEGF-Alo/+), and wild-type VEGF activity to thoracolumbar irradiation. Results: In rat spinal cord, the number of cells expressing HIF1α and VEGF increased rapidly from 16 to 20 weeks after radiation, before white matter necrosis and forelimb paralysis. A steep dose response was observed in expression of HIF1α and VEGF. HIF1α and VEGF expressing cells were identified as astrocytes. Hypoxia was present in regions where up-regulation of VEGF and glucose transporter-1 and increased permeability was observed. VEGF-Alo/+ mice had a longer latency to development of hindlimb weakness and paralysis compared with wild-type or VEGF-Ahi/+ mice. Conclusions: VEGF expression appears to play an important role in CNS radiation injury. This focuses attention on VEGF and other genes induced in response to hypoxia as targets for therapy to reduce or prevent CNS radiation damage.