tbuckley/cabot-search huggingface dataset:
The role of cholinergic supersensitivity in the medical symptoms associated with withdrawal of antipsychotic drugs
Authors: D J Luchins, W J Freed, R J Wyatt
Journal: American Journal of Psychiatry (1980)

From a review of the clinical literature, the authors determined that the medical symptoms of neuroleptic withdrawal occurred more frequently with neuroleptics having potent anticholinergic effects than with those having weak anticholinergic actions. When antiparkinsonian agents were not simultaneously withdrawn, there was a striking difference between these two categories of neuroleptics. Experiments with mice showed that withdrawal of haloperidol, a neuroleptic with weak anticholinergic effects, produced subsensitivity (depression of locomotor activity and seizure thresholds) to the cholinergic effects of physostigmine. These findings support the theory that the medical side effects of neuroleptic withdrawal are due to rebound cholinergic hypersensitivity associated with the anticholinergic actions of these drugs, rather than being related to their dopamine-blocking activity.
Lesson of the week: Hypopituitarism after coronary artery bypass grafting Commentary: Hypoadrenalism should also be considered in cases of persistent hyponatraemia
Authors: J S Davies, M F Scanlon, P E Belchetz
Journal: BMJ (1998)

Male erectile dysfunction-defined as "the inability to achieve or maintain an erection sufficient for sexual intercourse"-is one of the most common sexual dysfunctions in men. 1 Although erectile dysfunction can be primarily psychogenic in origin, most patients have an organic disorder, commonly with some psychogenic overlay. 1 Some men assume that erectile failure is a natural part of the aging process and tolerate it; for others it is devastating.Withdrawal from sexual intimacy because of fear of failure can damage relationships and have a profound effect on overall wellbeing for the couple. 2Since erectile dysfunction often accompanies chronic illnesses, such as diabetes mellitus, heart disease, hypertension, and a variety of neurological diseases, physicians from many medical disciplines will see patients with this disorder. 3 MethodsThe publications comprising this review were selected from a formal search of the full Medline database (using the terms erectile dysfunction, impotence, and penile erection).
Abstract 12767: Syndecan-4 Regulates Myocardial Stiffness by Inducing Myofibroblast Differentiation, Extracellular Matrix Production and Collagen Cross-linking in Response to Pressure Overload
Authors: Kate M Herum, Ida G Lunde, Biljana Skrbic, Theis Tonnessen, William E Louch, Almira Hasic, Ivar Sjaastad, Sigurd Boye, Sverre-Henning Brorson, Andreas Unger, Wolfgang A Linke, Maria F Gomez, Geir Christensen
Journal: Circulation (2013)

Pressure overload of the heart leads to remodeling of the left ventricle (LV) involving excessive production of extracellular matrix (ECM) by activated cardiac fibroblasts that differentiate into c...
Effect of the all trans retinoic acid (ATRA) on the differentiation, invasion and growth, in 3D culture and in vivo, of the murine mammary cell lines LM38. (FIRCA R03 TW007207)
Authors: Laura Todaro, Maria Veloso, Eduardo Farias, Lydia Puricelli, Rafael Mira-y-Lopez, Elisa Bal de Kier Joffe
Journal: Cancer Research (2007)

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

3046 

ATRA regulates growth, differentiation and apoptosis in different cellular types. Previously we demonstrated that ATRA treatment inhibited growth in monolayer of mammary lines LM38-HP (constituted by epithelioid cells), LM38-D2 (myoepithelial clone) and LM38-LP (containing both cellular types). Now we are evaluating the effect of ATRA in differentiation, survival and invasion of LM38 cells in three-dimensional matrigel cultures as well as in vivo growth and dissemination. For in vitro studies, cells grown for 3 days in matrigel were treated or not with 1uM ATRA for 2 additional days. Colonies were marked with different antibodies and analysed by confocal microscopy. The bicellular line LM38-LP developed polarized colonies (GM130, Golgi marker) with acinar structure. ATRA maintained the polarity and induced an increase in E-cadherin expression and reorganization. ATRA also induced a decrease of myoepithelial cells, indicated by the lower expression of the myoepithelial marker CK14 in the periphery of the colonies. Treatment with ATRA also increased the expression of activated Caspase 3 and promoted the nuclear translocation of p27 in the colony center, suggesting arrest of cellular cycle and induction of death. On the other hand, LM38-HP cells generated starry colonies without lumen and variable size, without polarized cells, even though ATRA induced an increase of activated Caspase 3. LM38-D2 cells organized in colonies with variable size and form without lumen or polarization. Treatment with ATRA showed a decrease in the expression of CK14 as well as and an increase of activated Caspase 3 together with the nuclear translocation of p27. In all cases ATRA treatment induced a reduction in colony size. In vivo studies were curried out employing LM38-LP cell line due to its ability to growth as invasive primary tumor and to metastasize lung. Cell were inoculated s.c. in Balb/c mice and when tumours were palpable, oral treatment with ATRA (2 mg/animal, twice a week) was administered for 15 days. A significant decrease in tumor growth, local invasion and the number and size of pulmonary metastasis was observed in ATRA treated mice 40 days after inoculation (p < 0,05). Besides, ATRA reduced invasion in matrigel (transwell) of all cellular lines, showing its most marked effect on the mixed LM38-LP (64% less than control, p < 0,05). Our results suggest that interactions between luminal and myoepithelial cells are necessary to accentuate the effect of ATRA in differentiation, death, invasion and metastatic dissemination.
Abstract 3026: MicroRNA Expression Profiling in the Ischemic Preconditioned Heart: Functional Role of a MiR-1/GATA-4/MiR-144, -451, and -762 Circuit
Authors: Pengyuan Zhang, Jing Chen, Xiaoping Ren, Xiaohong Wang, Evangelia G Kranias, Mario Medvedovic, Guo-Chang Fan
Journal: Circulation (2009)

While a wealth of data has uncovered a distinctive microRNA (miRNA) expression pattern that occurs in the setting of physiological and pathological stress, relatively little is known about miRNA re...
Efficacy of the DAC inhibitor LBH589 in both rituximab-sensitive and rituximab-resistant lymphomas and effect on the antitumor activity of chemotherapy agents, monoclonal antibodies, and bortezomib
Authors: I. Maraj, F. J. Hernandez-Ilizaliturri, M. Chisti, M. S. Czuczman
Journal: Journal of Clinical Oncology (2009)

8576 Deacetylases (DACs) are enzymes that remove the acetyl groups from target proteins [histones (class I) and non-histones (class II)], leading to regulation of gene transcription and other cellular processes. LBH589 is a novel and potent DAC class I and II Inhibitor undergoing pre-clinical and clinical testing. In order to develop therapeutic options for refractory/resistant B-cell lymphomas we studied the effects of LBH589 in the anti-tumor activity of chemotherapy agents and monoclonal antibodies in a panel of rituximab-sensitive cell lines (RSCL), rituximab-resistant cell lines (RRCL), and in lymphoma cells isolated from patients with treatment-naïve or refractory/relapsed B-cell lymphomas by negative selection using magnetic beads. NHL cells lines were exposed to the following chemotherapy agents or monoclonal antibodies: CDDP, doxorubicin, vincristine, bortezomib or rituximab, veltuzumab, or isotype, alone or in combination with LBH589. In dose-sequence studies the treatment with LBH589 preceded or followed in vitro exposure to the chemotherapy agent or the monoclonal antibody by 24 hrs. Changes in mitochondrial potential were determined by alamar blue reduction using a kinetic assay. Patient-derived tumor cells were exposed to either LBH589, bortezomib or both. Changes in ATP content were determined by cell titer glow assay. RNA was isolated from NHL cell lines exposed to LBH859 and changes in gene expression of the Bcl-2 family members were determined by qualitative polymerase chain reaction (PCR). LBH589 was active as a single agent against RSCL, RRCL or patient-derived tumor cells. In addition, Bcl-XL gene down-regulation was observed following exposure to LBH859. Synergistic activity was observed by combining LBH589 and chemotherapy agents, bortezomib or either of the two anti-CD20 mAbs studied. The sequence of administration impacted the degree of antitumor activity observed. Our data suggests that LBH589 is active against various RSCL, RRCL and patient-derived tumor cells. Findings suggest that LBH589 added to systemic anti-CD20 and/or chemotherapy could result in a novel and potent treatment strategy against B-cell lymphomas. No significant financial relationships to disclose.
Gemcitabine as an endovesical treatment in patients with BCG-refractory superficial bladder carcinoma
Authors: R. Gunelli, G. L. Frassineti, N. Giovannini, W. Zoli, M. Fiori, D. Amadori, P. Fabbri, E. Bercovich
Journal: Journal of Clinical Oncology (2005)

4706 Background: Transurethral resection is the first-line treatment of superficial bladder cancer (Ta-T1 stages), but about two-thirds of patients develop recurrences. For these patients, intravesical immunotherapy with Bacillus Calmette Guérin (BCG) is the most effective therapeutic and prophylactic approach, but one-third are destined to relapse. Therefore the search for active cytotoxic drugs remains an important goal. Gemcitabine (GEM) has proven to be effective in advanced bladder cancer patients when administered systemically and is also active, with minimal bladder irritation, in instillation treatment. Methods: A preclinical study was performed on bladder cancer lines (MCR and HT1376) and primary cultures to define the best treatment schedule with GEM. Results showed a synergic interaction from two 1-h exposures to GEM spaced apart by a 24-h drug washout. On the basis of these results and of the proven efficacy and safety of systematically administered GEM, we activated a phase II clinical trial using intravesical instillation therapy. The primary objective is to evaluate the percentage of disease-free patients at a median follow-up of 1 year after the start of therapy. The treatment schedule consists of weekly (days 1 and 3) instillations of 2000 mg of GEM diluted in 50 ml of saline solution, for six cycles. A recruitment of 45 patients with intermediate-high risk BCG-refractory superficial bladder cancer has been planned. Results: To date, 32 patients (2 with TaG3 multifocal tumors, 15 with T1G2 multifocal tumors and 15 with T1 G3 lesions) have been enrolled and all have completed the six instillation cycles. At a median follow-up of 14 months, 3 patients relapsed after 6 months, 2 after 9 months and one after 12 months, with an infiltrating lesion. Treatment was generally well tolerated: transitory hyperpyrexia (<38°) was observed in 6 patients and moderate dysuria was registered in 13 patients. A reduction in the drug dosage, in accordance with the protocol, was required in only one patient due to local toxicity. Conclusions: Although preliminary results are promising, a longer follow up is needed to confirm the efficacy of this treatment. Supported by National Research Council project no.02.000278.ST87 No significant financial relationships to disclose.
Abstract 4875: The Micro RNA but not the Messenger RNA Signature of Failing Human Hearts is Reversed by Mechanical Unloading
Authors: Scot J Matkovich, Kenneth B Margulies, Keith A Youker, Guillermo Torre-Amione, Derek J Van Booven, Gerald W Dorn
Journal: Circulation (2008)

Clinical and experimental congestive heart failure (CHF) is characterized by a program of regulated messenger RNA (mRNA) gene transcripts. Much is known about transcriptional control of cardiac gene expression in CHF, but less is known about the alternate mechanism of mRNA stability and translation by micro RNAs (miR). Specifically lacking is information on possible dynamic regulation of miRs during CHF treatment, and the effect on target mRNAs. Methods : We performed comprehensive microarray analyses of both mRNA transcript and miR levels in myocardial specimens from CHF without (n=16) or after (n=10) mechanical unloading with left ventricular assist devices (LVAD), in comparison to 7 non-failing hearts. Individual myocardial RNA samples were hybridized to NCode v2 arrays (Invitrogen, 467 human miRs) and Affymetrix HuEx v1.0 arrays (&gt;1 million exon clusters representing 290,000 full-length mRNAs). miR data were analyzed by a dye swap, loop design algorithm (NCode Profiler) after quality control; mRNA data were analyzed with Partek GS v6.3. Results : Of 467 miRs represented on arrays, 106 were reliably detected in nonfailing and failing hearts, representing cardiac-expressed miRs. Of these, 21 miRs (19.8%) were significantly (P&lt;0.05) regulated &gt;1.5-fold in CHF; 12 of these were increased &gt;10-fold. Hierarchical clustering showed no specific pattern of regulated miRs. Strikingly, all 21 significantly regulated miRNAs reverted toward nonfailing levels in the post-LVAD hearts (P&lt;0.05 vs CHF) with complete normalization observed for 5 miRs. In contrast, of 755 mRNAs that were altered by &gt;1.3-fold in failing hearts, 38% remained uncorrected post-LVAD. Neither the miR nor mRNA signatures differed between ischemic and nonischemic hearts, suggesting that the RNA profiles reflected advanced CHF, rather than a specific disease etiology. Conclusions : There is a distinct miR signature of end-stage heart failure that is reversible with mechanical unloading. This contrasts with mRNA profiles from the same hearts in which only a fraction of dysregulated mRNAs were normalized by LVAD support. Our findings suggest that regulation of translation by miR may account for some of the discordance between transcriptional and other phenotypic responses to LVAD support.
Abstract A27: Redefining the role of Notch in acinar to ductal metaplasia
Authors: Christopher J. Halbrook, Howard C. Crawford
Journal: Cancer Research (2015)

Abstract The EGFR and Notch signaling pathways have been widely implicated in relation to both chronic pancreatitis and pancreatic ductal adenocarcinoma in humans, however the link between the two pathways has remained obscure. Acinar to ductal metaplasia (ADM,) a phenomenon where acinar cells undergo a morphological change and begin expressing markers normally found only in ductal cells while losing markers typical of acinar cells, has been linked to both the Notch and EGFR signaling pathways. ADM is highly proliferative with the potential to develop into pancreatic intraepithelial neoplasia, a precursor lesion to pancreatic cancer. Recently we and others have shown that genetic ablation of EGFR in the pancreas effectively prevents acinar to ductal metaplasia in cerulein model of pancreatitis in mice, and prevents tumorigenesis driven by oncogenic Kras. Additionally, we have found that acinar cells harvested from EGFRf/f;Ptf1aCre/+ mice (EKO) mice are resistant to ADM in vitro upon cerulein treatment, or by the expression of oncogenic Kras. Activation of EGFR by treatment of WT collagen embedded acinar cell explants with the EGFR ligand TGF-α has previously been shown to induce ADM in a manner requiring Notch pathway activation. Furthermore, it has also been demonstrated that expression of Notch2 intracellular domain (N2ICD) is sufficient to induce ADM in WT acinar cells. To directly investigate the relationship of the EGFR, Kras, and Notch signaling pathways in ADM, we examined the effect of Notch signaling in acinar cells harvested from EKO mice. Interestingly, these acinar cells fail to transdifferentiate in vitro upon transduction of N2ICD in 3D culture; however the transdifferentiation event can be rescued by co-expression of oncogenic Kras with N2ICD in acinar cells lacking EGFR. These results indicate that EGFR is important in Notch induced ADM, however there are other pathways that possibly can be utilized by acinar cells expressing oncogenic Kras to drive ADM. Citation Format: Christopher J. Halbrook, Howard C. Crawford. Redefining the role of Notch in acinar to ductal metaplasia. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A27.
Abstract #5599: Boronated epidermal growth factor as a molecular targeting agent for neutron capture therapy of EGFR positive gliomas
Authors: Rolf Barth, Weilian Yang, Tianyao Huo, Werner Tjarks, Michael Ciesielski, Robert Fenstermaker, Peter Binns, Kent Riley
Journal: Cancer Research (2009)

The gene encoding epidermal growth factor receptor (EGFR) and its mutant isoform, EGFRvIII, frequently are overexpressed in gliomas and both are low or undetectable in normal brain. Based on these differences in receptor expression, we have carried out studies using either boronated EGF or anti-EGFR monoclonal antibodies (mAbs) as delivery agents for boron neutron capture therapy. BNCT is based on the selective uptake of sufficient amounts of boron-10 by tumor cells, followed by irradiation with low energy, thermal neutrons. The resulting nuclear capture and fission reactions produce high-energy \#945; particles and recoiling  7 Li nuclei. In the present study, we have evaluated a boronated dendrimer-epidermal growth factor (BD-EGF) bioconjugate as a molecular targeting agent for BNCT of the human EGFR gene-transfected F98 rat glioma, designated F98 EGFR . EGF was chemically linked to a heavily boronated polyamide amine dendrimer by means of the heterobifunctional reagent, mMBS, and boron was quantified by direct current plasma-atomic emission spectroscopy. Biodistribution studies were carried out at 6 h and 24 h following intratumoral (i.t.) injection or convection enhanced delivery (CED) of  125 I-labeled or unlabeled BD-EGF (40µg  10 B/ 10 µg EGF) to F98 glioma bearing rats. At 6 h., the amounts of radioactivity localized in EGFR (+) and (-) gliomas were similar following either i.t. injection or CED. However, at 24 h. there was 43% more radioactivity in EGFR(+) tumors following CED compared to i.t. injection, and a doubling of the tumor boron concentration (22.3 µg/g vs. 11.7 µg/g). CED of BD-EGF resulted in a 6.5x increase in the volume of distribution within the infused cerebral hemisphere and a 1.8x increase in tumor uptake of BD-EGF compared with i.t. injection, thereby demonstrating the superiority of CED as a mode of administration of the bioconjugate. BNCT studies were carried out in F98 EGFR  glioma bearing rats at the Massachusetts Institute of Technology nuclear reactor (MITRII) 24 h. after CED of BD-EGF. Animals that received BD-EGF, followed by BNCT, had a MST of 54.1 ± 4.7 d compared to 43.0±2.8 d. with i.t. injection. Rats that received BD-EGF by CED in combination with i.v. boronophenylalanine (BPA) had a MST of 86.0 ± 28.1 d compared to 39.8 ± 1.6 d for i.v. BPA alone (p versus  116% for CED of BD-EGF and 72 % for i.t. injection of BD-EGF. The test for equality of the survival curves indicated that overall, the differences were highly significant (p   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5599.
Exhibition: Duchenne and Gachet
Authors: A. K Banerjee
Journal: BMJ (1999)

“Duchenne de Boulogne: la mecanique des passions” is at the Ecole nationale superieure des Beaux-arts, Paris, until 4 April, and “Un ami de Cezanne et Van Gogh: le docteur Gachet” is at the Grand Palais, Paris, until 26 April 

Guillaume Duchenne, born in Boulogne in 1807, studied medicine in Paris and came under the spell of Laennec, Dupuytren, and Magendie and eventually specialised in neurology. He was unconventional and eccentric and never held a hospital appointment. He discovered that external electrical …
多关节肿痛-软组织肿胀-皮下结节
Authors: 何志斌, 沈敏
Journal: BMJ (2011)

患者女性，45岁，因“关节肿痛1年，加重4个月”于2010年3月23日入院。患者1年前无诱因突然出现双膝关节肿痛伴活动受限，左手第3掌指关节（MCP3）疼痛并伸直受限，伴足背局部肿胀，无晨僵、发热。症状持续1—2d能自行缓解，间断发作数次。4个月前出现双手近端间关节（PIP）、掌指关节、腕、肘、肩、膝、踝等多关节发作性疼痛，
Abstract 38: Demonstration of Mitochondrial Membrane Depolarization with FRET Spectroscopy in the Intact Heart
Authors: Sverre E Aune, Thomas L Clanton, Mark G Angelos
Journal: Circulation (2007)

Current methods for real time detection of mitochondrial membrane depolarization in the intact heart are very limited. Objective: To utilize fluorescence resonance energy transfer (FRET) as a sensi...
The Pathology of Neoatherosclerosis in Human Coronary Implants
Authors: Gaku Nakazawa, Fumiyuki Otsuka, Masataka Nakano, Marc Vorpahl, Saami K. Yazdani, Elena Ladich, Frank D. Kolodgie, Aloke V. Finn, Renu Virmani
Journal: Journal of the American College of Cardiology (2011)
IL-21 regulates the levels of key transcriptional factors in U937 leukemia cells
Authors: Chantel F. Fuqua, Richard Akomeah, Samuel E. Adunyah
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5999 

IL-21 is a cytokine produced by activated CD4+ T cells and expressed in lymphoid tissues. IL-21 has an effect on the growth, survival, and activation of B, T, and NK cells. It has been suggested that IL-21 induces the activation of JAK kinases and MAP kinases, thereby influencing other molecular mechanisms in the cell. Yet IL-21 has been shown to induce apoptosis in B cells. Since IL-21 affects the responses of several immune cells, it may be a beneficial treatment for the regulation of the immune system in asthma and cancer patients. Currently, the effects and mechanisms of IL-21 remain unclear and require further investigation. In this study we examined the effects of IL-21 on transcriptional regulation in U937 leukemia cells using DNA/Protein Transcriptional Array Techniques. We observed that IL-21 downregulates a number of key transcriptional factors including STAT4 (2.8-fold), C-myc (4.5-fold), p53 (3.3-fold), MEF-1 (3.4-fold), TR (DR-4) (3.7-fold), AP-2(2.4-fold) and Smad3/4(1.7-fold), though other preliminary result indicates that it may be activating STAT-1. These results suggest that the mechanisms of IL-21 perhaps involve transcriptional regulation of key transcriptional factors. Further studies are in progress to elucidate the mechanisms by which IL-21 regulates transcriptional activation and influences cell growth and survival. Supported by NCI/NIGMS SPORE.