tbuckley/cabot-search huggingface dataset:
Abstract 14398: Prospective Evaluation of Defibrillation Threshold and Post-shock Rhythm in Young ICD Recipients: High-energy Defibrillation and Post-shock Pacing May Not be Necessary
Authors: Andrew E Radbill, John K Triedman, Charles I Berul, Edward P Walsh, Mark E Alexander, Gregory Webster, Frank Cecchin
Journal: Circulation (2010)

Introduction: Adaptation of transvenous or entirely subcutaneous ICD systems to the needs of pediatric and congenital heart patients is problematic due to constraints of vascular and thoracic anato...
Vaccination with trastuzumab epitope mimics leads to prolonged tumor-free survival in HER-2/neu transgenic mice
Authors: Angelika B. Riemer, Kira H. Brämswig, Elena Quaglino, Guido Forni, Hubert Pehamberger, Otto Scheiner, Christoph C. Zielinski, Erika Jensen-Jarolim
Journal: Cancer Research (2006)

638  Passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin®) to date is the most effective treatment for patients with HER-2/neu overexpressing breast cancer. In previous studies we could show that active immunization with peptide mimotopes, i.e. structural mimics of the epitope recognized by trastuzumab, leads to formation of antibodies again recognizing HER-2/neu in mice. Functional in vitro analyses of the induced antibodies demonstrated ‘trastuzumab-like’ properties, such as receptor internalization, inhibition of signaling, and antibody-mediated cytotoxicity against HER-2/neu overexpressing breast cancer cells. The aim of the present study was to test the effects of trastuzumab mimotope vaccination in vivo, namely in a HER-2/neu transgenic mouse model. We used BALB-neuT mice, which carry the activated neu oncogene on the BALB/c background. These mice constitute the most aggressive animal model for HER-2/neu driven carcinogenesis, as all females uniformly develop mammary carcinomas at the age of 12 weeks. One group of mice was immunized with the previously described trastuzumab mimotope - KLH conjugate, a control group with the carrier protein KLH alone, and a further control group was left naive. Mice were palpated weekly to monitor tumor development and size, and blood samples were taken at regular intervals to follow up the induced immune responses. We found that trastuzumab mimotope immunizations lead to delayed tumor development and thus to an increase in tumor-free survival. When tumors occurred, they were smaller and grew more slowly than in the control mice. In contrast, control KLH immunizations did not affect tumor growth kinetics as compared to the naive mice. Serum analysis demonstrated that all immunized animals had mounted an anti-KLH immune response, so we accredit the observed tumor-inhibitory effects in the mimotope group to the biologic properties of induced anti-HER-2/neu antibodies. We conclude that epitope-specific vaccination with mimotopes elicits trastuzumab-like antibodies that are effective against HER-2/neu overexpressing tumor cells both in vitro and in vivo.
Relative efficacy of haloperidol and pimozide in children and adolescents with Tourette's disorder
Authors: F R Sallee, L Nesbitt, C Jackson, L Sine, G Sethuraman
Journal: American Journal of Psychiatry (1997)

The authors evaluated the relative efficacy and safety of pimozide and haloperidol in the treatment of Gilles de la Tourette's syndrome in children and adolescents.A double-blind, 24-week, placebo-controlled double crossover study of equivalent dose formulations of haloperidol and pimozide was conducted with 22 subjects, aged 7-16 years, with Tourette's disorder who were randomly assigned to first one active drug treatment and then the other. Biweekly assessment and flexible dose titration mimicked clinical practice. The primary outcome variable was total score on the Tourette Syndrome Global Scale. Final outcome was determined after 6 weeks of each treatment (placebo, pimozide, haloperidol), with a 2-week placebo baseline period and intervening 2-week placebo washout periods between treatments.Pimozide proved significantly different from placebo in affecting the primary outcome variable, whereas haloperidol failed to have a significant effect. Haloperidol exhibited a threefold higher frequency of serious side effects and significantly greater extrapyramidal symptoms relative to pimozide. Haloperidol-associated treatment-limiting adverse events were experienced by 41% of the patients. The therapeutic doses of pimozide and haloperidol were equivalent (mean = 3.4 mg/day, SD = 1.6, and mean = 3.5 mg/day, SD = 2.2, respectively).At equivalent doses, pimozide is superior to haloperidol for controlling symptoms of Tourette's disorder in children and adolescents.
Optical imaging of breast tumors with novel glucosamine-bound near-infrared probes
Authors: Cong Li, Tiffany Greenwood, Kristine Glunde
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4746 

Imaging lysosomes in breast tumors in vivo has great potential for assessing the metastatic and invasive potential of breast cancers since lysosomes play a major role in cancer invasion and matastasis by mediating protease routing, regulation, and secretion. We have synthesized two novel near-infrared (NIR) optical imaging probes (IR-1 and IR-2) for noninvasive imaging of lysosomes. These two probes contain an NIR emitting indocyanine moiety covalently bound to glucosamine through two different extended carbon chain linkers. IR-1 and IR-2 showed maximal absorbance at 766 and 768 nm, and emission at 782 and 784 nm, respectively, as determined by photospectroscopic measurements under physiological conditions. Both NIR dyes demonstrated higher quantum yields (Φf = 0.185 for IR-1, 0.113 for IR-2) than their precursor IR-783 (0.035) in aqueous solution. IR-2 exhibited a reversible fluorescence enhancement upon acidification in the pH range 4.0-7.2, which may be useful in future lysosome imaging studies because of the low lumenal pH in lysosomes. In vitro cytotoxicity of IR-1 and IR-2 in four human mammary epithelial cell (HMEC) lines: MDA-MB-435, MDA-MB-231, MCF-7, and MCF-12A, which represent different stages of malignancy, was determined to be very low in the concentration range typically used for in vivo optical fluorescence imaging (0.1-600 μM). Specific targeting of these NIR dyes to the lysosomal compartment was demonstrated by colocalization of immunofluorescently labeled lysosomal marker proteins, such as CD63 and lysosome-associated membrane proteins, with the NIR fluorescence in these four HMEC lines from IR-1 and IR-2. Dynamic live cell NIR fluorescence imaging showed that intracellular vesicle structures, most likely to be lysosomes, were visualized following incubation of these HMEC lines with IR-1 or IR-2 for 12 hours or longer with a concentration as low as 20 μM. In vivo noninvasive optical imaging and ex vivo biodistribution studies in tumor-bearing severe combined immunodeficient mice (SCID) showed that significant uptake of both NIR dyes occurred in orthotopic MDA-MB-435, MDA-MB-435, and MCF-7 tumor xenografts. The tumor/muscle ratios of IR-1 and IR-2 in MCF-7 tumors were as high as 5.9 and 7.4 respectively at 48 hours following systemic administration of 10 μmol/kg NIR dye. IR-1 and IR-2 may be very useful as NIR fluorescing contrast agents to assess the metastatic potential and to follow lysosomal trafficking in breast tumors in vivo . Grant support: NIH R21 CA112216. We thank Dr. Paul Winnard Jr., Dr. Noriko Mori, and Dr. Yoshinori Kato for technical assistance.
Abstract 293: Therapeutic effects of the bromodomain inhibitors JQ1 and I-BET 762 on pancreatic cancer
Authors: Ana S. Leal, Charlotte R. Williams, Michael B. Sporn, Karen T. Liby
Journal: Cancer Research (2015)

Abstract Pancreatic cancer is expected to be the second most deadly cancer by 2030 with very few effective therapeutic options to improve patient survival. Bromodomain inhibitors (JQ1 and I-BET 762) are a new generation of chemotherapeutic drugs that target BET proteins, impairing their ability to bind to acetyl modified lysines and therefore interfering with transcriptional initiation and elongation. BET proteins regulate several genes responsible for cell cycle, apoptosis and inflammation. I-BET 762 is currently in clinical trials for cancer and has the advantage of oral administration. Kras is one of the most common mutated genes in pancreatic cancer (90%); however its protein is a difficult drug target. p-Erk, responsible for several pathways regulating cell survival, is a downstream effector of Kras that has been shown to be essential for the progression and maintenance of pancreatic cancer. LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) and LSL-KrasG12D/+;Pdx-1-Cre (KC) mouse models are commonly used to study pancreatic cancer. KPC mice develop the full spectrum of pancreatic cancer by an average age of 20 weeks. The KC mouse model is commonly used to study pancreatic cancer progression after stimulation with a pancreatic inflammatory agent, such as cerulein. JQ1 and I-BET 762 reduce the protein levels of p-ERK 1/2 in cells lines derived from a pancreatic tumor or ascites of KPC animals. JQ1 and I-BET 762 are also effective at inhibiting cell growth in human pancreatic cells harboring Kras mutations. When KC mice are injected with LPS to induce inflammation and pancreatitis, p-ERK 1/2 protein levels are significantly increased. This model is being used to test the effects of JQ1 and I-BET 762 after a single LPS injection, in KC mice. Pancreatic cancer is driven by several cytokines and chemokines, including CCL2 and IL-6, which recruit and regulate the inflammatory cells (macrophages, T cells and MDSC (Myeloid derived suppressor cells) cells) in the tumor. Levels of IL-6 and CCL2 in cell lines developed from KPC mice are reduced when treated with JQ1 and I-BET 762. KC mice stimulated with LPS also have higher levels of CCL2 and IL-6 than mice stimulated with saline. In conclusion this study showed that the bromodomain inhibitors JQ1 and I-BET 762 had positive effects in suppressing targets of inflammation in pancreatic cancer. We thank James Bradner for the generous gift of JQ1. Citation Format: Ana S. Leal, Charlotte R. Williams, Michael B. Sporn, Karen T. Liby. Therapeutic effects of the bromodomain inhibitors JQ1 and I-BET 762 on pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 293. doi:10.1158/1538-7445.AM2015-293
Psychiatric Research Interview for Substance and Mental Disorders (PRISM): reliability for substance abusers
Authors: D S Hasin, K D Trautman, G M Miele, S Samet, M Smith, J Endicott
Journal: American Journal of Psychiatry (1996)

The purpose of this study was to investigate the reliability of a new semistructured diagnostic interview, the Psychiatric Research Interview for Substance and Mental Disorders (PRISM), for substance-abusing patients. The reliability of psychiatric diagnoses for individuals who drink heavily or use drugs has been shown to be problematic. The PRISM was designed to improve the reliability for such individuals.A test-retest reliability study of the PRISM was conducted with 172 patients being treated in dual-diagnosis or substance abuse settings.Good to excellent reliability was shown for many diagnoses, including affective disorders, substance use disorders, eating disorders, some anxiety disorders, and psychotic symptoms. The interview has recently been updated for DSM-IV diagnoses.The PRISM offers a method of producing psychiatric diagnoses with improved reliability for patients and other research subjects who have problems with alcohol or drugs.
Activation of Rabbit Platelets by Platelet-Activating Factor Derived from IgE-Sensitized Basophils
Authors: Peter M. Henson
Journal: Journal of Clinical Investigation (1977)

Platelet-activating factor (PAF) is liberated from antigen-stimulated, IgE-sensitized rabbit basophils and induces aggregation of platelets and secretion of their content of vasoactive amines. Experiments were performed to determine the relationship between these two platelet responses to this stimulus.(a) Aggregation was initiated by appreciably lower concentrations of PAF than were required to produce even minimal release of constituents. PAF-induced aggregation was also resistant to agents which destroy ADP, such as creatine phosphate/creatine phosphokinase or apyrase, and occurred with platelets made unresponsive (refractory) to ADP. It was concluded that PAF can induce aggregation by a mechanism which is distinguishable from the release reaction and from the aggregating effect of ADP.(b) Secretion can probably occur independently of aggregation because incubation without agitation resulted in secretion without detectable aggregation.(c) Despite the suggestion that the two platelet responses can be independent, they may be induced by the same stimulus. This was indicated by experiments in which platelets specifically desensitized to PAF-induced secretion were also found to be unresponsive to PAF-stimulated aggregation. Moreover, identical levels of inhibition and identical inhibition profiles were obtained for both responses with serine esterase inhibitor, diisopropylphosphofluoridate, and with amino acid esters. It was concluded that the same stimulus-specific activable protease (esterase) was most likely involved in PAF-induced aggregation and secretion.
Transcriptomic based Biomarkers Contain Diagnostic and Prognostic Information about Patients with new onset Heart Failure
Authors: Bettina Heidecker
Journal: Circulation (2007)

Abstract 1753 Bettina Heidecker, University of Miami, Miller School of Med, Miami, FL; Kenneth L Baughman, Brigham and Women’s Hosp, Boston, MA; Edward K Kasper, Ilan S Wittstein, Elayne Breton, Johns Hopkins Hosp, Baltimore, MD; Joshua M Hare, University of Miami, Miller School of Medicine, Miami, FL Bettina Heidecker, 2007 Finalist and Presenting Author
Controversies in Management: Medical treatment works for those with clear diagnosis
Authors: R C Spiller
Journal: BMJ (1994)

### Medical treatment works for those with clear diagnosis

Imprecise and inconsistent definition of the irritable bowel syndrome has created much confusion. A clear definition has, however, recently been agreed.1 The Rome consensus states that symptoms should be chronic and recurring and consist of abdominal pain that is clearly related to bowel function, being either relieved by defecation or associated with a change in frequency or consistency of stool with or without disturbed defecation, which is defined as two or more of the following: altered stool frequency, altered stool form (hard, loose, or watery), altered stool passage (straining, urgency, or feeling of incomplete defecation), and passage of mucus. The above symptoms are usually associated with bloating or a sense of abdominal distension. The syndrome excludes painless constipation and diarrhoea and also chronic abdominal pain that is unrelated to bowel movement in which psychiatric features predominate.

Irritable bowel symptoms are experienced by 8-22% of the population,2 but most learn to cope with their symptoms and less than one third actually consult a doctor. Consulters differ from non-consulters in being less easily reassured and more anxious, depressive, and prone to multiple complaints.2 3 4 This pattern is …
针对优化药物治疗仍高血糖的2型糖尿患者的营养干预随机对照研究（LOADD）——糖尿病生活方式高于药物治疗（摘要）
Authors: Kirsten, Coppell, Minako, Kataoka, Sheila, Williams, Alex, Chisholm, Sue, Vorgers, Jim, Mann, 闵锐, 李玉秀
Journal: BMJ (2010)
Common Cold Treatment Using Zinc—Reply
Authors: Rashmi Ranjan Das, Meenu Singh
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
APC determines histone deacetylases inhibitor-induced apoptosis in colon cancer cells
Authors: Tianying Zhu, Bin Guo
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4638 

Inhibitors of histone deacetylases (HDAC) are promising new drugs for various types of cancers. These agents inhibit malignant cell growth and induce apoptosis through unknown mechanisms. Here we report that the expression status of adenomatous polyposis coli (APC) protein determines whether colon cancer cells undergo apoptosis when treated with HDAC inhibitor Valproic acid (VPA). We used three colon cancer cell lines, LS174-T (expressing wild-type APC and β-catenin), SW620 and HT-29 (both expressing mutant APC), to investigate the role of APC in cell death induced by VPA. VPA induced apoptosis in LS174-T cells but not in SW620 or HT-29 cells. When wild-type APC protein was expressed using an inducible expression system, HT-29 cells underwent apoptosis in response to VPA. Conversely, knocking-down of APC protein by siRNA rendered LS174-T cells resistant to VPA-induced apoptosis. APC mediated VPA-induced apoptosis through down-regulation of Survivin. The level of Survivin protein decreased after VPA treatment in LS174-T and HT-29/APC cells, but not in SW620 and HT-29/β-Gal cells. While knocking-down of Survivin by siRNA sensitized SW620 cells to VPA-induced apoptosis, overexpression of Survivin blocked VPA-induced apoptosis in LS174-T cells. The data suggest that APC is a critical determinant of VPA-induced apoptosis in colon cancer cells and Survivin is a potential target to enhance cell death induced by VPA. As APC is frequently mutated in human colon cancers, these results have clear clinical indications.
测定血清S100蛋白用于诊断克-雅病:前瞻性病例对照研究
Authors: Markus, Otto, Jens, Wiltfang, Ekkehard, Schtz, Ingo, Zerr, Anke, Annette, Pfahlberg, Olaf, Gefeller, Manfred, Armin, Giese, Thomas, Weber
Journal: BMJ (1998)

目的:分析克-雅病(Creutzfeldt-Jakob dis-ease,CJD)患者及对照组血清中脑特异性 S100蛋白浓度。设计:前瞻性病例对照研究。研究单位:国家 CJD 监测站。研究对象:224例疑为 CJD 的转诊患者及35例无痴呆的对照病例。主要结果测定:CJD 患者、其他疾病引起的痴呆患者及对照组血清 S100浓度。结果:224例疑为 CJD 的患者中,65例经病理证实确诊;6例有基因突变而肯定诊断;43例很可能患 CJD;36例可能患 CJD;74例患有其他疾病。108例为肯定或很可能 CJD 患者,其血清 S100浓度中位数为395 pg/ml(SD 387 pg/ml)。这明显高于患其他疾病的74例患者(S100浓度中位数为109pg/ml,SDl77pg/ml;P=0.0001)。以213pg/ml为界值,S100测定用于 CJD 诊断的敏感性为77.8%(95%的可信区间为66.8%～85.2%),特异性为81.1%(70.3%～89.3%)。在 Kaplan-Meier 曲线上,不同浓度 S100患者的存活时间差异有显著性(P=0.023)。结论:S100血清浓度测定是一种有价值的工具,在 CJD 的鉴别诊断中,较测定脑脊液更有价值。尚需更多的研究以确定连续测定是否有助于提高此病的诊断准确性。
Glucocorticoid-induced tumor necrosis factor receptor–related protein co-stimulation facilitates tumor regression by inducing IL-9–producing helper T cells
Authors: Il-Kyu Kim, Byung-Seok Kim, Choong-Hyun Koh, Jae-Won Seok, Jun-Seok Park, Kwang-Soo Shin, Eun-Ah Bae, Ga-Eun Lee, Hyewon Jeon, Jaebeom Cho, Yujin Jung, Daehee Han, Byoung S Kwon, Ho-Young Lee, Yeonseok Chung, Chang-Yuil Kang
Journal: Nature Medicine (2015)
Tissue-specific transgenic mouse model experiments demonstrate that IGFBP2 actively contributes to glioma development and progression
Authors: Sarah M. Dunlap, Joseph Celestino, Eric C. Holland, Gregory N. Fuller, Wei Zhang
Journal: Cancer Research (2006)

4843   Insulin-like growth factor binding protein 2 (IGFBP2) has recently been shown to be overexpressed in 80% of the most advanced type of diffuse glioma, glioblastoma multiforme (GBM), by combined cDNA microarray and tissue microarray approaches. Furthermore, overexpressed IGFBP2 correlates with poor survival in diffuse gliomas.  In vitro  functional studies have provided evidence that IGFBP2 increases glioma cell migration and invasion. We therefore hypothesize that IGFBP2 is a key regulator of glioma progression. We tested our hypothesis using the somatic gene transfer RCAS-tva mouse model system, which permits the introduction of specific genes into specific cell lineages. In this system, avian virus receptor is expressed exclusively in glial cells via linkage to the neuroglial-specific nestin promoter. Genes of interest are cloned into an avian RCAS vector and viral particles are expanded in DF1 avian fibroblasts. When injected into the neonatal mouse brain, the virions infect only glial cells and the genes of interest borne by the virions are thus only expressed in glial cells. For these experiments, the study genes were  IGFBP2 , platelet-derived growth factor ( PDGF ),  K-Ras , and  Akt , which were delivered separately and in combination. Our results show that PDGF signaling leads exclusively to the formation of low-grade (WHO grade II) oligodendrogliomas. PDGF delivered in combination with IGFBP2 results in the formation of anaplastic oligodendrogliomas (WHO grade III). These higher-grade tumors are characterized by increased cellular density, vascular proliferation, and poor survival. Combined K-Ras and Akt leads to the formation of astrocytomas; K-Ras alone or Akt alone do not result in tumor formation. IGFBP2 in combination with K-Ras produces astrocytomas, which are histologically similar to the gliomas resulting from K-Ras/Akt stimulation. No tumor formation resulted from the simultaneous delivery of Akt and IGFBP2, suggesting that IGFBP2 and Akt likely lie in the same pathway or in converging pathways. The present studies show that: 1) IGFBP2 is associated with progression from low-grade O to high-grade AO in gliomas initiated by PDGFb overexpression  in vivo , and 2) IGFBP2 can synergize with the Ras pathway to produce diffuse gliomas  in vivo . Collectively, the data demonstrate that IGFBP2 actively contributes to diffuse glioma initiation and progression. Studies are ongoing to further elucidate the signaling pathways of IGFBP2-induced gliomagenesis.
The combination of lithium carbonate and an MAOI in refractory depressions
Authors: S Fein, V Paz, N Rao, J LaGrassa
Journal: American Journal of Psychiatry (1988)

Lithium combined with phenelzine alleviated the symptoms of four severely depressed patients. Previously, all four patients had failed to respond to tricyclic antidepressants, and three had not responded to monoamine oxidase inhibitors.
Protein truncation test of LYST reveals heterogenous mutations in patients with Chediak-Higashi syndrome
Authors: Stéphanie Certain, Franck Barrat, Elodie Pastural, Françoise Le Deist, Jose Goyo-Rivas, Nada Jabado, Malika Benkerrou, Reinhard Seger, Etienne Vilmer, Gilles Beullier, Klaus Schwarz, Alain Fischer, Geneviève de Saint Basile
Journal: Blood (2000)