tbuckley/cabot-search huggingface dataset:
Post-transcriptional regulatory network of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions
Authors: Fei Guo, Brittany C Parker Kerrigan, Da Yang, Limei Hu, Ilya Shmulevich, Anil K Sood, Fengxia Xue, Wei Zhang
Journal: Journal of Hematology & Oncology (2014)

Epithelial-to-mesenchymal transition (EMT) and its reverse process, mesenchymal-to-epithelial transition (MET), play important roles in embryogenesis, stem cell biology, and cancer progression. EMT can be regulated by many signaling pathways and regulatory transcriptional networks. Furthermore, post-transcriptional regulatory networks regulate EMT; these networks include the long non-coding RNA (lncRNA) and microRNA (miRNA) families. Specifically, the miR-200 family, miR-101, miR-506, and several lncRNAs have been found to regulate EMT. Recent studies have illustrated that several lncRNAs are overexpressed in various cancers and that they can promote tumor metastasis by inducing EMT. MiRNA controls EMT by regulating EMT transcription factors or other EMT regulators, suggesting that lncRNAs and miRNA are novel therapeutic targets for the treatment of cancer. Further efforts have shown that non-coding-mediated EMT regulation is closely associated with epigenetic regulation through promoter methylation (e.g., miR-200 or miR-506) and protein regulation (e.g., SET8 via miR-502). The formation of gene fusions has also been found to promote EMT in prostate cancer. In this review, we discuss the post-transcriptional regulatory network that is involved in EMT and MET and how targeting EMT and MET may provide effective therapeutics for human disease.
The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach
Authors: Z W Zhang, S E Patchett, D Perrett, P H Katelaris, P Domizio, M J G Farthing
Journal: Gut (1998)

Vitamin C may be protective against gastric cancer though infection with Helicobacter pylori is associated with a reduction in intragastric concentrations of vitamin C.To examine the effects of H pylori infection, gastric juice pH, the severity and extent of gastric inflammation, and CagA antibody status of the individual on gastric juice and mucosal vitamin C concentrations.One hundred and fifteen patients undergoing routine gastroscopy for investigation of dyspepsia.High performance liquid chromatography was used to determine vitamin C concentrations. CagA antibody was detected by western blot analysis.Gastric juice ascorbic acid concentration was significantly lower in patients infected with H pylori compared with those uninfected (19.3 mumol/l (interquartile range (IQR) 10.7-44.5) versus 66.9 mumol/l (IQR 24.4-94.2), p = 0.003). The reduction in gastric juice ascorbic acid concentration was inversely related to the severity of gastritis (p = 0.01). CagA positive patients had significantly lower gastric juice ascorbic acid concentrations than CagA negative ones (14.8 mumol/1 (IQR 7.9-52.2) versus 39 mumol/l (IQR 19.9-142.2), p = 0.05). Decreased gastric juice dehydroascorbic acid concentrations were observed in patients with gastric atrophy and intestinal metaplasia. Mucosal ascorbic acid concentrations were also significantly lower in infected patients than uninfected patients (p = 0.04).The reduction in gastric vitamin C concentrations is related to gastric juice pH, the severity and extent of gastritis, the presence of H pylori, and the CagA antibody status of the individual. These findings may have implications in H pylori associated carcinogenesis.
Fv structure of monoclonal antibody II-481 against herpes simplex virus Fc gamma-binding glycoprotein gE contains immunodominant complementarity determining region epitopes that react with human immunoglobulin M rheumatoid factors.
Authors: P J Johansson, C Malone, W Swietnicki, B M Dunn, R C Williams
Journal: The Journal of Experimental Medicine (1994)

Human immunoglobulin M (IgM) rheumatoid factors (RFs) show primary direct enzyme-linked immunosorbent assay (ELISA) reactivity with Fab rather than Fc fragments of monoclonal antibody (mAb) II-481 directed against the Fc gamma-binding site of herpes simplex virus glycoprotein gE. This preferential anti-Fab specificity suggests that RFs react with antigen-binding portions of mAb II-481 as anti-idiotypic antibodies directed at the combining site regions of mAb reacting with the Fc gamma-binding region of gE. Analysis of this idiotype-anti-idiotype reaction employed polymerase chain reaction amplification and sequencing of the variable heavy and light (VH and VL) regions of mAb II-481. When VH and VL regions of mAb II-481 were synthesized as overlapping 7-mer peptides on polypropylene pins, a panel of 10 polyclonal and 6 monoclonal human IgM RFs reacted primarily with epitopes within the three solvent-exposed mAb II-481 complementarity determining regions (CDRs). Preincubation of single CDR heptamer peptides with IgM RFs in free solution, resulted in 63-100% inhibition of RF binding to mAb II-481 on the ELISA plate, confirming the antigenic importance of linear CDR regions for RF reactivity. Combinations of two or three CDR peptides frequently produced 94-100% inhibition of RF binding to whole mAb II-481. Control peptides, singly or in combination, showed no inhibition. Computer modeling suggested that the RF-reactive mAb II-481 Fv region and a previously demonstrated RF-reactive CH3 epitope displayed considerable three-dimensional similarities in conformation. These studies may provide insight into limited shape homologies possibly involved in an RF anti-idiotypic reaction.
Initiating Insulin Therapy in Type 2 Diabetes
Authors: Philip Raskin, Elsie Allen, Priscilla Hollander, Andrew Lewin, Robert A. Gabbay, Peter Hu, Bruce Bode, Alan Garber
Journal: Diabetes Care (2005)

Safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 70/30, prebreakfast and presupper) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs (OADs).This 28-week parallel-group study randomized 233 insulin-naive patients with HbA(1c) values >/=8.0% on >1,000 mg/day metformin alone or in combination with other OADs. Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5-6 units BIAsp 70/30 twice daily or 10-12 units glargine at bedtime and titrated to target blood glucose (80-110 mg/dl) by algorithm-directed titration.A total of 209 subjects completed the study. At study end, the mean HbA(1c) value was lower in the BIAsp 70/30 group than in the glargine group (6.91 +/- 1.17 vs. 7.41 +/- 1.24%, P < 0.01). The HbA(1c) reduction was greater in the BIAsp 70/30 group than in the glargine group (-2.79 +/- 0.11 vs. -2.36 +/- 0.11%, respectively; P < 0.01), especially for subjects with baseline HbA(1c) >8.5% (-3.13 +/- 1.63 vs. -2.60 +/- 1.50%, respectively; P < 0.05). More BIAsp 70/30-treated subjects reached target HbA(1c) values than glargine-treated subjects (HbA(1c) </=6.5%: 42 vs. 28%, P < 0.05; HbA(1c) <7.0%: 66 vs. 40%, P < 0.001). Minor hypoglycemia (episodes/year) was greater in the BIAsp 70/30 group than in the glargine group (3.4 +/- 6.6 and 0.7 +/- 2.0, respectively; P < 0.05). Weight gain and daily insulin dose at study end were greater for BIAsp 70/30-treated subjects than for glargine-treated subjects (weight gain: 5.4 +/- 4.8 vs. 3.5 +/- 4.5 kg, P < 0.01; insulin dose: 78.5 +/- 39.5 and 51.3 +/- 26.7 units/day, respectively).In subjects with type 2 diabetes poorly controlled on OADs, initiating insulin therapy with twice-daily BIAsp 70/30 was more effective in achieving HbA(1c) targets than once-daily glargine, especially in subjects with HbA(1c) >8.5%.
Concordance of Genetic Alterations in Poorly Differentiated Colorectal Neuroendocrine Carcinomas and Associated Adenocarcinomas
Authors: A. O. Vortmeyer, I. A. Lubensky, M. J. Merino, C. Wang, T. Pham, Z. Zhuang, E. E. Furth
Journal: JNCI Journal of the National Cancer Institute (1997)

The histopathologic spectrum of colorectal neuroendocrine tumors ranges from benign to highly malignant. In this spectrum, poorly differentiated neuroendocrine carcinoma (PDNC) is the most aggressive type, characterized by early dissemination and a rapidly fatal course. Since it is unclear whether PDNC originates from neoplastic transformation of preexisting neuroectodermal cells, pluripotent epithelial stem cells, or adenocarcinoma precursor cells, we investigated the histogenesis of this type of cancer by performing genetic analyses on a series of colorectal tumors.Archived histologic sections of colorectal PDNC from nine patients were analyzed; gastrointestinal carcinoid tumor specimens from four patients were used as controls. The specimens were deparaffinized, microdissected, and analyzed genetically. After DNA extraction, polymerase chain reaction amplification was performed to investigate alteration (i.e., loss of heterozygosity [LOH]) of the APC (adenomatous polyposis coli), DCC (deleted in colorectal carcinoma), and p53 (also known as TP53) genes.LOH of the APC, DCC, or p53 genes was observed in six of eight informative PDNC tumors; no LOH was detected in the carcinoid control specimens. Four of five informative PDNC tumors had associated adenocarcinoma; LOH of the APC and p53 genes in these tumors involved the same allele in both tissue components. Four of the five tumors with associated adenocarcinoma showed LOH of the DCC gene; in three of these four tumors, the PDNC and adenomatous components showed LOH of the same allele.PDNC and associated adenocarcinoma appear to be derived from the same cell of origin, which is most likely either a pluripotent epithelial stem cell or an adenocarcinoma precursor cell.
THE USE OF FORCEPS AND CAESAREAN SECTION IN LABOUR
Authors: H. Chapple
Journal: BMJ (1930)

r HAE chosell for mily subject tlhe use -of forceps anul Caesarean section in lahour for l soveral reasons, the thlsief of wxhich is that unildel its cover I miay lprovokle dis- us.sion of cer taill mechianical prol)emxs that arise in coni- liexionl with cases of labc)our that 'may occur any1day ill anty li-actice..atlherthan detail a series of inidividulal cases, I thinik it wo-ould he mor e )rofitalNe if I attempted tI) reviewx labour as a whole, and(1 tr ied to estaliljshi prin- cilples which might guide us in imiakinig a `vise sclection of the uitse of forceps or Caesarean section, when either is no ess,ary.The gr-eat majority of cases require 1)0 sp)ecial muechamiical treatmiienlt at all, and imx them -ve mier-elv 'try to omtrol the pail) and safeguard thie patient avtailst anyrv possible avoid- atble accident.MTax 1 digfress fr-oiii the main themlie hele for just a imiomenit, because the importance of tlhe psychic si(le of labour is so ofteni completely ignored, anid wve, as a profession, do niot regard it ser iously elnouglh.To a great many patients tlxe expleriellce of labour is associated ith ghastly pain, anid the effect it pr-oduces uiponi their psychology is often ver-ihimarked.It is veryv imiiportanit in the pliesemit disecussion that x-e shlo-uld re'alize that tlhoughl olong ed laboumr may be physiological, it is exti enely iaiixful, and xx'e ixixist bear tlhat )oinit ,'ell in mliind if xv-e a.re to mllake a wvise (10oice in cases ii xxhich sumrgical initer- vention v-odl(l be called fior.Jiist as there is a breakinog straiii y-hiieh varies xvitlh the in(dividlulal miietal, so thiere is a' breaking, str ain in everv Iimiinaii iuemitalitv, amid it, too, varices xith the inidividual.Manyv of us xvere famiiiliar xxitlh cases of shell shock in the xvar; cases of birth slhock ar e jutst as real, but they oftexi pass unrecognized.It is xx-itli the consideration of cases ixi wlxieli labour is obstruiicted that -e tire noxx particularly concerned.
Altered gene expression in acute systemic inflammation detected by complete coverage of the human liver transcriptome
Authors: Cédric Coulouarn, Grégory Lefebvre, Céline Derambure, Thierry Lequerre, Michel Scotte, Arnaud Francois, Dominique Cellier, Maryvonne Daveau, Jean-Philippe Salier
Journal: Hepatology (2004)

The goal of the current study was to provide complete coverage of the liver transcriptome with human probes corresponding to every gene expressed in embryonic, adult, and/or cancerous liver. We developed dedicated tools, namely, the Liverpool nylon array of complementary DNA (cDNA) probes for approximately 10,000 nonredundant genes and the LiverTools database. Inflammation-induced transcriptome changes were studied in liver tissue samples from patients with an acute systemic inflammation and from control subjects. One hundred and fifty-four messenger RNAs (mRNA) correlated statistically with the extent of inflammation. Of these, 134 mRNA samples were not associated previously with an acute-phase (AP) response. The hepatocyte origin and proinflammatory cytokine responsiveness of these mRNAs were confirmed by quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR) in cytokine-challenged hepatoma cells. The corresponding gene promoters were enriched in potential binding sites for inflammation-driven transcription factors in the liver. Some of the corresponding proteins may provide novel blood markers of clinical relevance. The mRNAs whose level is most correlated with the AP extent (P <.05) were enriched in intracellular signaling molecules, transcription factors, glycosylation enzymes, and up-regulated plasma proteins. In conclusion, the hepatocyte responded to the AP extent by fine tuning some mRNA levels, controlling most, if not all, intracellular events from early signaling to the final secretion of proteins involved in innate immunity. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Avoidance of Cyclosporine in Renal Transplantation
Authors: HUONG T. B. TRAN, MURALIDHAR K. ACHARYA, DIANNE B. MCKAY, MOHAMED H. SAYEGH, CHARLES B. CARPENTER, HUGH AUCHINCLOSS, ROBERT L. KIRKMAN, EDGAR L. MILFORD
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Cyclosporine (CsA) has been implicated in both acute and chronic graft dysfunction. The addition of humanized IL-2 receptor antibody daclizumab (DZB) to CsA-based immunosuppression decreases the rate of acute renal transplant rejection. Therefore, 45 patients were evaluated in an immunosuppressive protocol that included DZB, mycophenolate mofetil (MMF), and steroids without CsA. This was a prospective, nonrandomized, open-label trial of the efficacy and safety of the treatment. DZB was given intravenously at 2 mg/kg before transplantation and then at 1 mg/kg every 2 wk for four doses, MMF was given orally at 3 g/d, and methylprednisolone/prednisone was given at 7 mg/kg per day and tapered to 15 mg/d at 6 mo. CsA was added to the regimen when patients developed acute rejection episodes or adverse effects to steroids or MMF; 49% of patients were spared CsA maintenance. Patients without CsA had lower serum creatinine at 6 mo and needed fewer medications to control BP. Incidence of biopsyproven rejections was 31% and occurred early (median, 10 d). These rejection episodes occurred earlier in cadaver transplants (median, 7 d) and later in living donor transplants (median, 62 days). Acute rejections occurred at a higher frequency (46% versus 34%) and earlier (6.5 versus 15 d) in patients with delayed graft function compared with patients without delayed graft function. Most of the rejections were moderate and easily reversible. The actuarial 1-yr graft survival was 95% with 100% patient survival.
Prevention of endogenous leukotriene production during anaphylaxis in the guinea pig by an inhibitor of leukotriene biosynthesis (MK-886) but not by dexamethasone.
Authors: A Guhlmann, A Keppler, S Kästner, H Krieter, U B Brückner, K Messmer, D Keppler
Journal: The Journal of Experimental Medicine (1989)

Leukotriene C4 (LTC4) underwent rapid elimination from the circulating blood and was extensively converted to LTD4 within the vascular space of the guinea pig. To mimic the elimination and metabolism of endogenous LTC4 generated during anaphylaxis, 14,15-3H-labeled LTC4 was infused intravenously over a period of 15 min, leading to a recovery in bile of 85% of the infused LT radioactivity within 2 h. Corresponding to the tracer studies, LTD4 and, to a lesser extent, LTC4 were the predominant endogenous cysteinyl LTs in guinea pig bile. The biliary production rate of endogenous LTD4 increased from 0.3 +/- 0.1 to 6.2 +/- 1.8 pmol x min-1 x kg-1 (p less than 0.001) during anaphylactic shock induced by intravenous injection of OVA (0.2 mg/kg) into sensitized guinea pigs. A novel LT biosynthesis inhibitor (MK-886; 10 mg/kg, i.v., 15 min before antigen challenge) suppressed the antigen-induced cysteinyl LT production by greater than 92% (p less than 0.001). This inhibition of systemic LTC4 formation was associated with a complete protection against lethal anaphylactic shock in animals pretreated in addition with the H1 receptor antagonist pyrilamine. Pretreatment with either the inhibitor of LT synthesis or the histamine receptor antagonist reduced the lethality during anaphylactic shock from 100 to 60 and 78%, respectively. In artificially ventilated, pyrilamine-pretreated animals, the antigen-induced decrease in dynamic lung compliance and the rise in hematocrit were significantly reduced (p less than 0.05) by pretreatment with the inhibitor of LT synthesis. Dexamethasone at high doses (10 mg/kg, i.p., once daily for 7 d, or in a single dose of 10 mg/kg, i.v., 3.5 h before challenge) had no inhibitory effect on LT generation during anaphylaxis in vivo. However, in resident peritoneal macrophages, harvested from these dexamethasone-treated sensitized guinea pigs and stimulated with zymosan, both cysteinyl LT and 6-keto-PGF1 alpha formation were strongly suppressed. These studies indicate an important role of cysteinyl LTs in systemic anaphylaxis in vivo and demonstrate the blockade of anaphylactic LT generation by a novel inhibitor of LT biosynthesis (MK-886) but not by dexamethasone.
Clonality in Acquired Hematologic Disorders
Authors: D G Gilliland, K L Blanchard, H F Bunn
Journal: Annual Review of Medicine (1991)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Inhibitor of Differentiation-1 as a Novel Prognostic Factor in NSCLC Patients with Adenocarcinoma Histology and Its Potential Contribution to Therapy Resistance
Authors: Mariano Ponz-Sarvisé, Paul A. Nguewa, María J. Pajares, Jackeline Agorreta, María D. Lozano, Miriam Redrado, Ruben Pio, Carmen Behrens, Ignacio I. Wistuba, Carlos E. García-Franco, Jesús García-Foncillas, Luis M. Montuenga, Alfonso Calvo, Ignacio Gil-Bazo
Journal: Clinical Cancer Research (2011)

Abstract Purpose: High inhibitor of differentiation-1 (Id1) levels have been found in some tumor types. We aimed to study Id1 levels and their prognostic impact in a large series of stages I to IV non-small cell lung cancer (NSCLC) patients. Experiments in cell lines and cells derived from malignant pleural effusions (MPE) were also carried out. Experimental Design: A total of 346 NSCLC samples (three different cohorts), including 65 matched nonmalignant tissues, were evaluated for Id1 expression by using immunohistochemistry. Additional data from a fourth cohort including 111 patients were obtained for Id1 mRNA expression analysis by using publicly available microarrays. In vitro proliferation assays were conducted to characterize the impact of Id1 on growth and treatment sensitivity. Results: Significantly higher Id1 protein levels were found in tumors compared with normal tissues (P &amp;lt; 0.001) and in squamous carcinomas compared with adenocarcinomas (P &amp;lt; 0.001). In radically treated stages I to III patients and stage IV patients treated with chemotherapy, higher Id1 levels were associated with a shorter disease-free survival and overall survival in adenocarcinoma patients in a log-rank test. A Cox model confirmed the independent prognostic value of Id1 levels for both stages I to III and stage IV patients. In silico analysis confirmed a correlation between higher Id1 mRNA levels and poor prognosis for adenocarcinoma subjects. In vitro Id1 silencing in radio/chemotherapy-resistant adenocarcinoma cells from MPEs restored sensitivity to both therapies. Conclusions: In our series, Id1 levels showed an independent prognostic value in patients with adenocarcinoma, regardless of the stage. Id1 silencing may sensitize adenocarcinoma cells to radiotherapy and chemotherapy. Clin Cancer Res; 17(12); 4155–66. ©2011 AACR.
Oocyte-granulosa cell interactions
Authors: R. Canipari
Journal: Human Reproduction Update (2000)

In the past, different protocols of ovulation induction, aimed to overcome problems of anovulatory infertility in humans, have been developed during IVF programmes. However, administration of exogenous hormones may cause severe health problems, e.g. ovarian hyperstimulation syndrome. To overcome this problem an attractive alternative is to develop in-vitro systems that allow follicle and oocyte growth and maturation. This paper reviews the current status of research on oocyte–granulosa cell interactions and on the autocrine and paracrine factors involved in follicle development. The ovarian follicle is a morphological and functional unit in which the somatic and germ cell components are intimately associated and interdependent. The co-ordinate development of follicle and oocyte leads to a number of modifications in the growing oocyte necessary for the acquisition of competence to mature correctly and to undergo fertilization and embryo development. The search for the optimal culture conditions and the correct balance of hormones necessary to obtain a fertilizable oocyte in vitrois extremely important for clinical and agricultural applications.
Peritraumatic Reactions Associated With the World Trade Center Disaster
Authors: Daphne Simeon, Jennifer Greenberg, Margaret Knutelska, James Schmeidler, Eric Hollander
Journal: American Journal of Psychiatry (2003)

The World Trade Center disaster was of unprecedented magnitude and impact in U.S. history. The authors conducted a pilot survey investigating these effects.A questionnaire regarding the disaster was sent to responders to an advertisement. It included demographic and disaster-exposure questions and three scales applied to "during and shortly after" the disaster.Despite widely ranging exposure, scores for distress (Peritraumatic Distress Inventory), dissociation (Peritraumatic Dissociative Experiences Questionnaire), and posttraumatic stress (Impact of Event Scale-Revised) were markedly elevated (N=75). After covariance for exposure, the distress factor of loss of control most strongly predicted both early dissociation and posttraumatic stress. Life threat specifically contributed to arousal. Dissociation did not contribute beyond distress to posttraumatic stress, with the exception of re-experiencing.This survey of reactions to the World Trade Center disaster revealed high levels of early symptoms and suggested similar but independent pathways toward dissociation and posttraumatic stress.
Predicting domain-domain interactions using a parsimony approach.
Authors: Katia S Guimarães, Raja Jothi, Elena Zotenko, Teresa M Przytycka
Journal: Genome biology (2006)

We propose a novel approach to predict domain-domain interactions from a protein-protein interaction network. In our method we apply a parsimony-driven explanation of the network, where the domain interactions are inferred using linear programming optimization, and false positives in the protein network are handled by a probabilistic construction. This method outperforms previous approaches by a considerable margin. The results indicate that the parsimony principle provides a correct approach for detecting domain-domain contacts.