tbuckley/cabot-search huggingface dataset:
Physiologic Levels of 2-Methoxyestradiol Interfere with Nongenomic Signaling of 17β-Estradiol in Human Breast Cancer Cells
Authors: Veena Vijayanathan, Sripriya Venkiteswaran, Sandhya K. Nair, Arti Verma, T.J. Thomas, Bao Ting Zhu, Thresia Thomas
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The purpose of this investigation is to determine the effects of physiologic levels (10-50 nmol/L) of 2-methoxyestradiol (2ME) on the growth of estrogen receptor (ER)–positive breast cancer cells and provide insights into its mechanism(s) of action. Experimental Design: Using the ERα-positive breast cancer cells, we studied the effects of 2ME on cell proliferation and cell signaling. Our hypothesis is that 17β-estradiol (E2) and 2ME can affect shared cell signaling pathways, leading to different outcomes in cell proliferation, depending on the absence/presence of E2. Results: E2 stimulated the growth of MCF-7 and T-47 D cells and induced Akt phosphorylation, a nongenomic signaling pathway. In the absence of E2, 10 to 50 nmol/L of 2ME enhanced cell growth and Akt phosphorylation. However, in the presence of E2, 2ME inhibited E2-induced cell growth and prevented E2-induced Akt phosphorylation. Confocal microscopic studies showed that 2ME inhibited subcellular distribution of ERα in response to E2 in MCF-7 and T-47D cells. 2ME also down-regulated E2-induced increases in cyclic AMP and ornithine decarboxylase activity. In addition, treatment of MCF-7 cells with 2ME in the presence of E2 resulted in a decrease in ERα level by 72 hours. Accelerated down-regulation of ERα may contribute to growth inhibition in the presence of E2/2ME combinations. In contrast, a concentration of up to 2.5 μmol/L 2ME had no effect on the growth of ER-negative SK-BR-3 cells, either in the presence or absence of E2. Conclusions: Our results provide evidence for the nongenomic action of 2ME in ER-positive cells. In the presence of E2, 2ME suppressed E2-induced cell growth, Akt signaling, and generation of cyclic AMP, whereas it acted as an estrogen in the absence of E2. The intriguing growth-stimulatory and growth-inhibitory effects of 2ME on breast cancer cells suggests the need for its selective use in patients.
Salivary steroids and psychometric parameters in male marathon runners.
Authors: B Harris, N J Cook, R F Walker, G F Read, D Riad-Fahmy
Journal: British Journal of Sports Medicine (1989)

Testosterone and cortisol in male marathon runners (n = 11) were determined in saliva samples (n = 28) collected during the three rest days preceding a competitive marathon and in the samples collected at 08.00h on the race day. An Eysenck Personality Inventory was completed on the first rest day and psychological state was assessed on rest days and on the morning of the marathon by completion of visual analogue scales for anxiety, depression, hostility and libido at four times each day. Anxiety, depression and hostility were positively inter-correlated. Extraversion and depression were negatively correlated. At 08.00h on the day of the marathon, anxiety and hostility scores were significantly higher than those on rest days, but depression and libido scores were unchanged. No relationship was found between depression or libido and any hormonal parameter. Race day cortisol correlated negatively with hostility, and changes in cortisol (09.00h) between the race day and the mean rest-day levels correlated with the corresponding changes in anxiety.
Combination of Proteasome and HDAC Inhibitors for Uterine Cervical Cancer Treatment
Authors: Zhenhua Lin, Martina Bazzaro, Mei-Cheng Wang, Kwun C. Chan, Shiwen Peng, Richard B.S. Roden
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Cervical cancer cells are addicted to the expression of the human papillomavirus (HPV) oncoproteins E6 and E7. The oncogencity of E6 is mediated in part by targeting p53 and PDZ-family tumor suppressor proteins for rapid proteasomal degradation, whereas the E7 oncoprotein acts in part by coopting histone deacetylases (HDAC)1/2. Here, we examine the hypothesis that inhibition of proteasome function and HDAC activity would synergistically and specifically trigger cervical cancer cell death by the interruption of E6 and E7 signaling. Experimental Design: The sensitivity and molecular responses of keratinocytes and HPV-positive and HPV-negative cervical cancer cells and xenografts to combinations of proteasome and HDAC inhibitors were tested. The expression of HDAC1/HDAC2 in situ was examined in cervical cancer, its precursors, and normal epithelium. Results: Cervical cancer cell lines exhibit greater sensitivity to proteasome inhibitors than do HPV-negative cervical cancers or primary human keratinocytes. Treatment of cervical cancer cells with bortezomib elevated the level of p53 but not hDlg, hScribble or hMAGI. Immunohistochemical analysis revealed elevated HDAC1/HDAC2 expression in cervical dysplasia and cervical carcinoma versus normal cervical epithelium. The combination of bortezomib and HDAC inhibitor trichostatin A or vorinostat shows synergistic killing of HPV-positive, but not HPV-negative, cervical cancer cell lines. Similarly, treatment of HeLa xenografts with the combination of bortezomib and trichostatin A retarded tumor growth significantly more effectively than either agent alone. Conclusions: A combination of proteasome and HDAC inhibitors, including bortezomib and vorinostat, respectively, warrants exploration for the treatment of cervical cancer.
CD40 induces human multiple myeloma cell migration via phosphatidylinositol 3–kinase/AKT/NF-κB signaling
Authors: Yu-Tzu Tai, Klaus Podar, Nicholas Mitsiades, Boris Lin, Constantine Mitsiades, Deepak Gupta, Masaharu Akiyama, Laurence Catley, Teru Hideshima, Nikhil C. Munshi, Steven P. Treon, Kenneth C. Anderson
Journal: Blood (2003)
Radiofrequency catheter ablation of sustained intra-atrial reentrant tachycardia in adult patients. Identification of electrophysiological characteristics and endocardial mapping techniques.
Authors: S A Chen, C E Chiang, C J Yang, C C Cheng, T J Wu, S P Wang, B N Chiang, M S Chang
Journal: Circulation (1993)

BACKGROUND Information about electrophysiological characteristics and radiofrequency ablation of intra-atrial reentrant tachycardia has not been reported before. We proposed that induction and termination of intra-atrial reentrant tachycardia by atrial extrastimuli or rapid atrial pacing and resetting the response pattern by atrial extrastimuli during intra-atrial reentrant tachycardia could ensure the mechanism of reentry and that the earliest site of endocardial activation and concealed entrainment pace mapping with the shortest stimulus-P wave interval could localize a critical area responsible for intra-atrial reentrant tachycardia and radiofrequency ablation. METHODS AND RESULTS Seven patients with refractory atrial tachycardia were referred for electrophysiological studies and radiofrequency ablation. Electrophysiological studies and endocardial mapping found (1) 10 atrial foci with atrial tachycardia cycle length of 406 +/- 41 ms; (2) atrial tachycardia had induction and termination by atrial extrastimuli (8 of 10) or rapid atrial pacing (10 of 10); (3) atrial tachycardia had increasing (6 of 10) or mixed (flat and increasing, 4 of 10) resetting response pattern, with resetting interval of 57 +/- 13 ms (14 +/- 4% of atrial tachycardia cycle length); (4) exit sites of atrial tachycardia in right atrial free wall (6 of 10), right atrial septum (3 of 10), and midposterior left atrium (1 of 10); and (5) earliest activation site had timing relative to P wave by -37 +/- 7 ms, and concealed entrainment pace mapping had shortest stimulus-P interval 23 +/- 3 ms. By the endocardial activation pace-mapping technique, radiofrequency energy (8 +/- 1 pulses, 31 +/- 3 W, 101 +/- 11 seconds) successfully eliminated the 10 atrial foci without recurrence (follow-up, 16 +/- 5 months). CONCLUSIONS Mechanism of intra-atrial reentrant tachycardia could be confirmed by the electrophysiological characteristics, and radiofrequency ablation energy delivered to a critical area in the atrial reentrant circuit is safe and effective for the treatment of intra-atrial reentrant tachycardia.
Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice
Authors: Jing Qing, Xiangnan Du, Yongmei Chen, Pamela Chan, Hao Li, Ping Wu, Scot Marsters, Scott Stawicki, Janet Tien, Klara Totpal, Sarajane Ross, Susanna Stinson, David Dornan, Dorothy French, Qian-Rena Wang, Jean-Philippe Stephan, Yan Wu, Christian Wiesmann, Avi Ashkenazi
Journal: Journal of Clinical Investigation (2009)

Overexpression of FGF receptor 3 (FGFR3) is implicated in the development of t(4;14)-positive multiple myeloma. While FGFR3 is frequently overexpressed and/or activated through mutations in bladder cancer, the functional importance of FGFR3 and its potential as a specific therapeutic target in this disease have not been elucidated in vivo. Here we report that inducible knockdown of FGFR3 in human bladder carcinoma cells arrested cell-cycle progression in culture and markedly attenuated tumor progression in xenografted mice. Further, we developed a unique antibody (R3Mab) that inhibited not only WT FGFR3, but also various mutants of the receptor, including disulfide-linked cysteine mutants. Biochemical analysis and 2.1-A resolution crystallography revealed that R3Mab bound to a specific FGFR3 epitope that simultaneously blocked ligand binding, prevented receptor dimerization, and induced substantial conformational changes in the receptor. R3Mab exerted potent antitumor activity against bladder carcinoma and t(4;14)-positive multiple myeloma xenografts in mice by antagonizing FGFR3 signaling and eliciting antibody-dependent cell-mediated cytotoxicity (ADCC). These studies provide in vivo evidence demonstrating an oncogenic role of FGFR3 in bladder cancer and support antibody-based targeting of FGFR3 in hematologic and epithelial cancers driven by WT or mutant FGFR3.
Immune complexes can trigger specific, T cell-dependent, autoanti-IgG antibody production in mice.
Authors: D A Nemazee
Journal: The Journal of Experimental Medicine (1985)

Immunization of mice with a combination of passively administered syngeneic IgG (anti-p-azophenylarsonate [anti-Ars]) antibody and a soluble, multivalent form of the antibody's corresponding antigen (Limulus polyphemus hemocyanin conjugated with Ars [Lph-Ars]) resulted in specific autoanti-IgG Fc (rheumatoid factor) production. The response was rapid and only anti-IgG of the IgM isotype is found. Because immunization with either the IgG antibody or the antigen alone did not result in rheumatoid antibody production, immune complexes appear to be the active form of the immunogens. Antibody/antigen ratios that resulted in maximal anti-IgG antibody responses were the same as those required for peak in vitro immunoprecipitation, i.e., equivalence. Previous exposure of the mice to the exogenously supplied antigen was not required for the response. The response to immune complexes is specific because mice immunized with IgG2a-containing complexes produced autoanti-IgG2a, while mice immunized with IgG1-containing complexes produced anti-IgG1 with little reactivity to other IgG isotypes. IgG2a blocked in its complement-fixing capacity was more effective in eliciting the anti-IgG2a response than native IgG2a, suggesting a possible role for the complement system in modulating the anti-IgG2a response. Induction of rheumatoid factor production by immune complexes could be induced in xid mice but not in nu/nu mice, indicating T lymphocyte dependence of the response. In contrast, the B lymphocyte activator lipopolysaccharide was able to elicit vigorous rheumatoid factor production in both nu/nu and normal mice, demonstrating that nu/nu mice contain B cells capable of making the response. Rheumatoid antibody produced in the immune complex- or LPS-induced responses is Fc specific and has relatively low affinity for IgG that is not bound to antigen.
Antigen- and receptor-driven regulatory mechanisms. I. Induction of suppressor T cells with anti-idiotypic antibodies.
Authors: M S Sy, B A Bach, Y Dohi, A Nisonoff, B Benacerraf, M I Greene
Journal: The Journal of Experimental Medicine (1979)

Delayed-type hypersensitivity (DTH) to the azobenzenearsonate (ABA) hapten can be readily induced in A/J mice injecting ABA-coupled syngeneic spleen cells subcutaneously. To further characterize this T-cell-dependent immunological phenomenon, the effect of passively administered anti-cross-reactive idiotype common to anti-ABA antibodies of A/J mice (CRI) antibodies on the development of ABA-specific DTH was investigated. Animals given daily injections (of minute amounts) of anti-CRI antibodies subsequent to immunization with ABA-coupled cells show significant reduction of ABA specific responses. This inhibition is antigen specific and requires the intact immunoglobulin molecule, as F(ab')2 treatments were ineffective in suppressing the reaction. Investigations of the mechanism of the anti-CRI-induced suppression of ABA DTH revealed that the observed suppression is a result of the activation of suppressor cells. Spleen cells taken from animals which received anti-CRI antibodies were able to adoptively transfer suppression to naive recipients. This suppression was shown to be mediated by T cells, as anti-Thy1.2 plus complement completely abrogated the transfer of suppression. In addition, animals pretreated with low doses of cyclophosphamide were not suppressed by the administration of anti-CRI antibodies. The genetic restriction of anti-CRI-induced suppression was demonstrated. Antibodies to the major cross-reactive idiotype, (CRI) associated with anti-ABA antibodies in A/J mice were unable to suppress the development of DTH to ABA in BALB/c mice (H-2d, Igh-1a). Such antibodies were, however, fully active in suppressing ABA DTH in the allotype-congenic C.AL-20 strain which has an allotype (Igh-1d) similar to that of A/J (Igh-1e) on a BALB/c background, and which produces humoral antibodies with the CRI.
Residual Gastric Content after Gastric Lavage and Ipecacuanha-Induced Emesis in Self-Poisoned Patients: An Endoscopic Study
Authors: J P Saetta, D N Quinton
Journal: Journal of the Royal Society of Medicine (1991)

Flexible endoscopy was used to assess the intragastric residue after either ipecacuanha-induced emesis or gastric lavage in 30 self-poisoned patients. Of the 13 patients treated by induced-emesis, five (38.5%) had residual solid in the stomach; 17 patients were treated by gastric washout, and 15 (88.2%) of these had residual intragastric solid. The study provides direct evidence that the gastric decontaminating procedures employed, and especially gastric lavage, do not remove stomach contents completely.
Methods for Incorporating the Hypermutability of CpG Dinucleotides in Detecting Natural Selection Operating at the Amino Acid Sequence Level
Authors: Y. Suzuki, T. Gojobori, S. Kumar
Journal: Molecular Biology and Evolution (2009)

In detecting natural selection operating at the amino acid sequence level by comparing the rates of synonymous (r(S)) and nonsynonymous (r(N)) substitutions, the rates of synonymous and nonsynonymous mutations are assumed to be approximately the same. In reality, however, these rates may not be the same if different proportions of synonymous and nonsynonymous sites overlap with CpG dinucleotides, which are known to be hypermutable in some organisms. Here, we develop the evolutionary pathway methods for comparing r(S) and r(N) at multiple codon sites (all-sites analysis) and at single codon sites (single-site analysis) that take into account the hypermutability at CpG dinucleotides in estimating the number of synonymous substitutions per synonymous site (d(S)) and nonsynonymous substitutions per nonsynonymous site (d(N)). Computer simulations show that the direction and magnitude of the bias in the estimation of d(N)/d(S) caused by the hypermutability of CpGs are determined by both the number of CpGs and the relative proportions of synonymous and nonsynonymous sites overlapping with CpGs. This bias is greatly reduced when using the methods we propose to account for the hypermutability of CpG dinucleotides. In an all-sites analysis of protamine 1 genes from primates, d(N)/d(S) > 1 was observed for many pairs if the hypermutability was ignored. However, d(N)/d(S) becomes <or=1 for most of these pairs when the CpG sites are assumed to be hypermutable. Therefore, statistical indications of positive selection in some sequences or individual codons may be caused by mutation rate differences in synonymous and nonsynonymous sites.
Tissue Plasminogen Activator Activates NF-κB through a Pathway Involving Annexin A2/CD11b and Integrin-Linked Kinase
Authors: Ling Lin, Chuanyue Wu, Kebin Hu
Journal: Journal of the American Society of Nephrology (2012)

NF-κB activation is central to the initiation and progression of inflammation, which contributes to the pathogenesis of CKD. Tissue plasminogen activator (tPA) modulates the NF-κB pathway, but the underlying mechanism remains unknown. We investigated the role of tPA signaling in macrophage NF-κB activation and found that tPA activated NF-κB in a time- and dose-dependent manner. tPA also induced the expression of the NF-κB–dependent chemokines IP-10 and MIP-1α. The protease-independent action of tPA required its membrane receptor, annexin A2. tPA induced the aggregation and interaction of annexin A2 with integrin CD11b, and ablation of CD11b or administration of anti-CD11b neutralizing antibody abolished the effect of tPA. Knockdown of the downstream effector of CD11b, integrin-linked kinase, or disruption of its engagement with CD11b also blocked tPA-induced NF-κB signaling. In vivo, tPA-knockout mice had reduced NF-κB signaling, fewer renal macrophages, and less collagen deposition than their counterparts. Taken together, these data suggest that tPA activates the NF-κB pathway in macrophages through a signaling pathway involving annexin A2/CD11b-mediated integrin-linked kinase.
Rapamycin Inhibits the Growth and Metastatic Progression of Non-Small Cell Lung Cancer
Authors: Daniel J. Boffa, Fulung Luan, Dolca Thomas, Hua Yang, Vijay K. Sharma, Milagros Lagman, Manikkam Suthanthiran
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Lung cancer has a dismal prognosis and comprises 5.5% of post-transplant malignancies. We explored whether rapamycin inhibits the growth and metastatic progression of non-small cell lung cancer (NSCLC). Experimental Design: Murine KLN-205 NSCLC was used as the model tumor in syngeneic DBA/2 mice to explore the effect of rapamycin on tumor growth and metastastic progression. We also examined the effect of rapamycin on cell cycle progression, apoptosis, and proliferation using murine KLN-205 NSCLC cells and human A-549 NSCLC cells as targets. The in vivo and in vitro effects of cyclosporine and those of rapamycin plus cyclosporine were also investigated. Results: Rapamycin but not cyclosporine inhibited tumor growth; s.c. tumor volume was 1290 ± 173 mm3 in untreated DBA/2 mice, 246 ± 80 mm3 in mice treated with rapamycin, and 1203 ± 227 mm3 in mice treated with cyclosporine (P &amp;lt; 0.001). Rapamycin but not cyclosporine prevented the formation of distant metastases; eight of eight untreated mice and four of six mice treated with cyclosporine developed pulmonary metastases whereas only one of six mice treated with rapamycin developed pulmonary metastases (P = 0.003). In vitro, rapamycin induced cell cycle arrest at the G1 checkpoint and blocked proliferation of both KLN-205 and A-549 cells but did not induce apoptosis. Cyclosporine did not prevent cell cycle progression and had a minimal antiproliferative effect on KLN-205 and A-549 cells. Conclusions: The immunosuppressive macrolide rapamycin but not cyclosporine prevents the growth and metastatic progression of NSCLC. A rapamycin-based immunosuppressive regimen may be of value in recipients of allografts.
Hong Kong Influenza
Authors: Malcolm I. Lindsay
Journal: JAMA (1970)

During an epidemic, in November and December 1968, the influenza A Hong Kong/68 virus was isolated from 127 adult patients. The procedures for isolation and identification of this virus are described. The clinical manifestations were similar to those of Asian influenza in 1957. Pneumonia was a complication in 20 cases. Based on roentgenograms, these cases were separated into the following two distinct syndromes: localized pneumonia (ten cases), either bacterial or viral, with low mortality (two deaths); and bilateral or diffuse pneumonia (ten cases), a primary influenza virus pneumonia, with high mortality (six deaths). Staphylococcus aureus or Pseudomonas aeruginosa infection was present in six of the eight fatal cases. Patients who were elderly, had associated chronic disease, or were hospitalized with other illnesses were most prone to develop pneumonia. Current methods of influenza control are discussed.
Effects of hypoxia, cyanide, and ischaemia on myocardial contraction: observations in isolated muscle and intact heart
Authors: F. A. PIRZADA, W. B. HOOD, J. V. MESSER, O. H. L. BING
Journal: Cardiovascular Research (1975)

Journal Article Effects of hypoxia, cyanide, and ischaemia on myocardial contraction: observations in isolated muscle and intact heart Get access FAROUK A. PIRZADA, FAROUK A. PIRZADA From the Tufts and Boston University Medical Services of the Boston City Hospital, and the Departments of Medicine, Tufts and Boston University Medical Schools, Boston, Mass, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar WILLIAM B. HOOD, JR., WILLIAM B. HOOD, JR. From the Tufts and Boston University Medical Services of the Boston City Hospital, and the Departments of Medicine, Tufts and Boston University Medical Schools, Boston, Mass, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar JOSEPH V. MESSER, JOSEPH V. MESSER From the Tufts and Boston University Medical Services of the Boston City Hospital, and the Departments of Medicine, Tufts and Boston University Medical Schools, Boston, Mass, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar OSCAR H. L. BING OSCAR H. L. BING 2 From the Tufts and Boston University Medical Services of the Boston City Hospital, and the Departments of Medicine, Tufts and Boston University Medical Schools, Boston, Mass, USA 2Present address: Presbyterian St Lukes Hospital, 1753 W. Congress St, Chicago, Illinois 60612, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 9, Issue 1, January 1975, Pages 38–46, https://doi.org/10.1093/cvr/9.1.38 Published: 01 January 1975
Relation between ectopic ossification after total hip arthroplasty and activity of general inflammation in patients with ankylosing spondylitis
Authors: Y. TANI, J. NISHIOKA, K. INOUE, S. HUKUDA, M. TSUJIMOTO
Journal: Annals of the Rheumatic Diseases (1998)

Ectopic ossification (EO) is a well known complication after total hip arthroplasty (THA). Some previous studies have considered ankylosing spondylitis (AS) a risk factor of EO, however other studies have refuted this association.1 The reported incidence of EO varies widely in different series.2 

We retrospectively studied a total of 20 primary THAs in 16 Japanese patients with definite AS. The age of the patients at surgery ranged from 30 to 64 years (mean 45). All THAs apart from three cases were performed using bone cement. Surgical exposure was achieved by the posterolateral approach. The length of follow up averaged 93 months (range 29 to 148). Compared with the incidence of EO in AS …