tbuckley/cabot-search huggingface dataset:
The Expression of Migration Stimulating Factor, a Potent Oncofetal Cytokine, Is Uniquely Controlled by 3′-Untranslated Region–Dependent Nuclear Sequestration of Its Precursor Messenger RNA
Authors: Richard A. Kay, Ian R. Ellis, Sarah J. Jones, Stéphane Perrier, Margaret M. Florence, Ana M. Schor, Seth L. Schor
Journal: Cancer Research (2005)

Migration stimulating factor (MSF) is a truncated oncofetal fibronectin isoform expressed by fetal and tumor-associated cells. MSF mRNA is distinguished from other fibronectin isoforms by its size (2.1 kb) and the inclusion of a specific intronic sequence at its 3' end. Initial Northern blot analysis with a MSF-specific probe indicated the presence of this 2.1-kb transcript and an additional unexpected 5.9-kb RNA present in both MSF-secreting (fetal) and nonsecreting (adult) fibroblasts. Our investigations into the nature of these transcripts and their relationship to MSF protein secretion revealed that the 5.9-kb mRNA is a second MSF-encoding transcript. Both these mRNAs have identical coding sequence and differ only in the length of their intron-derived 3'-untranslated region (UTR). The 5.9-kb MSF mRNA is retained in the nucleus whereas the 2.1-kb mRNA is not. MSF-secreting fetal fibroblasts have significantly lower nuclear levels of the 5.9-kb mRNA and correspondingly higher cytoplasmic levels of the 2.1-kb transcript than their nonsecreting adult counterparts. Adult fibroblasts induced to secrete MSF by treatment with transforming growth factor-beta1 displayed similar changes in their respective levels of MSF mRNA, but not those of a control gene. When cloned downstream of a reporter gene, only the longer 3'-UTR retained coding sequence within the nucleus. We conclude that expression of MSF protein is regulated by 3'-UTR truncation of the 5.9-kb nuclear-sequestered "precursor" MSF mRNA and nuclear export of mature 2.1-kb message. Inducible 3'-UTR processing represents a novel regulatory mechanism involved in cancer pathogenesis that may open new avenues for therapeutic gene delivery.
24-hour intragastric acidity and nocturnal acid secretion in patients with duodenal ulcer during oral administration of cimetidine and atropine.
Authors: R E Pounder, R H Hunt, S H Vincent, G J Milton-Thompson, J J Misiewicz
Journal: Gut (1977)

Cimetidine markedly inhibits gastric acid secretion, but from the therapeutic point of view it is important to know whether concurrent treatment with an anticholinergic increases its effect. This possibility has been investigated by measuring the 24 h intragastric acidity and nocturnal output of acid in four duodenal ulcer patients, each receiving on separate occasions cimetidine 1 g/day and placebo, atropine 2-4 mg/day and placebo, cimetidine and atropine, or two placebos. Cimetidine alone decreased mean hourly hydrogen ion activity by 63% of control values, decreased mean hourly hydrogen ion concentration (total acid) by 41%, inhibited nocturnal acid secretion by 83% and resulted in half the nocturnal samples being anacidic. Atropine alone had no effect when compared with control and combined treatment with both drugs was not superior to cimetidine alone. Atropine did not affect the absorption or urinary excretion of cimetidine. Fasting serum gastrin concentrations were not changed by any of the treatments. At the doses studied, the combination of cimetidine with an anticholinergic appears to offer no advantages over treatment with the H2-antagonist alone. Cimetidine is the only potent anti-secretory drug that does not cause acute side-effects and this important advantage would be lost if it were given with a maximal dose of an anticholinergic.
The MHC class I peptide repertoire is molded by the transcriptome
Authors: Marie-Hélène Fortier, Étienne Caron, Marie-Pierre Hardy, Grégory Voisin, Sébastien Lemieux, Claude Perreault, Pierre Thibault
Journal: The Journal of Experimental Medicine (2008)

Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I–associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that ∼25% of MHC I–associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K–AKT–mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I–associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells.
The Role of Metastasis-Associated Protein 1 in Prostate Cancer Progression
Authors: Matthias D. Hofer, Rainer Kuefer, Sooryanarayana Varambally, Haojie Li, Jing Ma, Geoffrey I. Shapiro, Juergen E. Gschwend, Richard E. Hautmann, Martin G. Sanda, Klaudia Giehl, Andre Menke, Arul M. Chinnaiyan, Mark A. Rubin
Journal: Cancer Research (2004)

Abstract Distinguishing aggressive prostate cancer from indolent disease represents an important clinical challenge, as current therapy requires over treating men with prostate cancer to prevent the progression of a few cases. Expression of the metastasis-associated protein 1 (MTA1) has previously been found to be associated with progression to the metastatic state in various cancers. Analyzing DNA microarray data, we found MTA1 to be selectively overexpressed in metastatic prostate cancer compared with clinically localized prostate cancer and benign prostate tissue. These results were validated by demonstrating overexpression of MTA1 in metastatic prostate cancer by immunoblot analysis. MTA1 protein expression was evaluated by immunohistochemistry in a broad spectrum of prostate tumors with tissue microarrays containing 1940 tissue cores from 300 cases. Metastatic prostate cancer demonstrated significantly higher mean MTA1 protein expression intensity (score = 3.4/4) and percentage of tissue cores staining positive for MTA1 (83%) compared with clinically localized prostate cancer (score = 2.8/4, 63% positive cores) or benign prostate tissue (score = 1.5/4, 25% positive cores) with a mean difference of 0.54 and 1.84, respectively (P &amp;lt; 0.00001 for both). Paradoxically, for localized disease, higher MTA1 protein expression was associated with lower rates of prostate specific antigen recurrence after radical prostatectomy for localized disease. In summary, this study identified an association of MTA1 expression and prostate cancer progression.
Human Gut Microbiome and Risk for Colorectal Cancer
Authors: Jiyoung Ahn, Rashmi Sinha, Zhiheng Pei, Christine Dominianni, Jing Wu, Jianxin Shi, James J. Goedert, Richard B. Hayes, Liying Yang
Journal: JNCI Journal of the National Cancer Institute (2013)

We tested the hypothesis that an altered community of gut microbes is associated with risk of colorectal cancer (CRC) in a study of 47 CRC case subjects and 94 control subjects. 16S rRNA genes in fecal bacterial DNA were amplified by universal primers, sequenced by 454 FLX technology, and aligned for taxonomic classification to microbial genomes using the QIIME pipeline. Taxonomic differences were confirmed with quantitative polymerase chain reaction and adjusted for false discovery rate. All statistical tests were two-sided. From 794217 16S rRNA gene sequences, we found that CRC case subjects had decreased overall microbial community diversity (P = .02). In taxonomy-based analyses, lower relative abundance of Clostridia (68.6% vs 77.8%) and increased carriage of Fusobacterium (multivariable odds ratio [OR] = 4.11; 95% confidence interval [CI] = 1.62 to 10.47) and Porphyromonas (OR = 5.17; 95% CI = 1.75 to 15.25) were found in case subjects compared with control subjects. Because of the potentially modifiable nature of the gut bacteria, our findings may have implications for CRC prevention.
Systemic lupus erythematosus in the elderly: clinical and immunological characteristics.
Authors: J Font, L Pallares, R Cervera, A Lopez-Soto, M Navarro, X Bosch, M Ingelmo
Journal: Annals of the Rheumatic Diseases (1991)

Systemic lupus erythematosus (SLE) predominantly affects young women in their 20s. In 40 out of 250 (16%) patients with SLE seen in our hospital disease onset occurred after the age of 50. The interval between the time of onset and diagnosis was five years in this older group compared with three years in the younger group. Arthritis, as a first symptom, was less common in the older onset group. During the follow up a lower incidence of arthritis, malar rash, photosensitivity, and nephropathy was found in the older onset group. In contrast, this group showed an increased incidence of myositis. High titres of anti-dsDNA tended to occur less often and the incidence of anti-Ro antibodies was lower in the older onset group. These features seem to distinguish patients with older onset SLE as a particular subset.
Association of Breast Cancer Stem Cells Identified by Aldehyde Dehydrogenase 1 Expression with Resistance to Sequential Paclitaxel and Epirubicin-Based Chemotherapy for Breast Cancers
Authors: Tomonori Tanei, Koji Morimoto, Kenzo Shimazu, Seung Jin Kim, Yoshio Tanji, Tetsuya Taguchi, Yasuhiro Tamaki, Shinzaburo Noguchi
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Breast cancer stem cells have been shown to be associated with resistance to chemotherapy in vitro, but their clinical significance remains to be clarified. The aim of this study was to investigate whether cancer stem cells were clinically significant for resistance to chemotherapy in human breast cancers. Experimental Design: Primary breast cancer patients (n = 108) treated with neoadjuvant chemotherapy consisting of sequential paclitaxel and epirubicin-based chemotherapy were included in the study. Breast cancer stem cells were identified by immunohistochemical staining of CD44/CD24 and aldehyde dehydrogenase 1 (ALDH1) in tumor tissues obtained before and after neoadjuvant chemotherapy. CD44+/CD24− tumor cells or ALDH1-positive tumor cells were considered stem cells. Results: Thirty (27.8%) patients achieved pathologic complete response (pCR). ALDH1-positive tumors were significantly associated with a low pCR rate (9.5% versus 32.2%; P = 0.037), but there was no significant association between CD44+/CD24− tumor cell proportions and pCR rates. Changes in the proportion of CD44+/CD24− or ALDH1-positive tumor cells before and after neoadjuvant chemotherapy were studied in 78 patients who did not achieve pCR. The proportion of ALDH1-positive tumor cells increased significantly (P &amp;lt; 0.001) after neoadjuvant chemotherapy, but that of CD44+/CD24− tumor cells did not. Conclusions: Our findings suggest that breast cancer stem cells identified as ALDH1-positive, but not CD44+/CD24−, play a significant role in resistance to chemotherapy. ALDH1-positive thus seems to be a more significantly predictive marker than CD44+/CD24− for the identification of breast cancer stem cells in terms of resistance to chemotherapy.
Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy.
Authors: J R Crossen, D Garwood, E Glatstein, E A Neuwelt
Journal: Journal of Clinical Oncology (1994)

PURPOSE To examine behavioral dimensions of treatment outcomes for patients receiving cranial irradiation. Radiation encephalopathy is one of these and refers to significant cognitive and emotional dysfunction following radiation therapy to the brain. Issues of definition, estimated incidence, pathophysiologic mechanisms, and recommended research designs are reviewed in relationship to functional neurobehavioral outcomes. PATIENTS AND METHODS Twenty-nine studies of adults receiving therapeutic cranial irradiation (TCI) involving 748 patients and 18 studies of prophylactic cranial irradiation (PCI) involving 368 patients are reviewed. Assessment of patient outcomes are summarized for research published since 1980, with specific attention to adverse changes in cognitive and emotional functioning. RESULTS Analyses revealed that 213 TCI patients and 100 PCI patients showed encephalopathy attributed to radiation. Manifestations of the late delayed effects of radiotherapy on brain function are related to patient age, total dose of irradiation, fraction sizes, and timing of chemotherapy. Radiation encephalopathy appears to be more common than the pathologic tissue injury of radiation necrosis. Accurate diagnosis of these neurobehavioral sequelae can require follow-up over a period of years with sensitive assessment procedures. CONCLUSIONS It is likely that the true incidence of treatment-related side effects of cranial irradiation in adults who survive more than 6 months without brain tumor growth or recurrence has been significantly underestimated. Research designs that include formal neuropsychologic assessment in conjunction with other neurodiagnostic tests can provide more comprehensive evaluation of long-term neurobehavioral outcomes.
PYODERMA GANGRENOSUM: THE HISTOLOGY OF THE PRIMARY LESION.*
Authors: G. H. PERCIVAL
Journal: British Journal of Dermatology (1957)

Journal Article PYODERMA GANGRENOSUM: THE HISTOLOGY OF THE PRIMARY LESION. Get access G. H. PERCIVAL G. H. PERCIVAL Edinburgh University Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 69, Issue 4, 1 April 1957, Pages 130–136, https://doi.org/10.1111/j.1365-2133.1957.tb13243.x Published: 01 April 1957
Gene expression analysis of nuclear factor I-A deficient mice indicates delayed brain maturation
Authors: Yong Wee Wong, Christian Schulze, Thomas Streichert, Richard M Gronostajski, Melitta Schachner, Thomas Tilling
Journal: Genome biology (2007)

Nuclear factor I-A (NFI-A), a phylogenetically conserved transcription/replication protein, plays a crucial role in mouse brain development. Previous studies have shown that disruption of the Nfia gene in mice leads to perinatal lethality, corpus callosum agenesis, and hydrocephalus.To identify potential NFI-A target genes involved in the observed tissue malformations, we analyzed gene expression in brains from Nfia-/- and Nfia+/+ littermate mice at the mRNA level using oligonucleotide microarrays. In young postnatal animals (postnatal day 16), 356 genes were identified as being differentially regulated, whereas at the late embryonic stage (embryonic day 18) only five dysregulated genes were found. An in silico analysis identified phylogenetically conserved NFI binding sites in at least 70 of the differentially regulated genes. Moreover, assignment of gene function showed that marker genes for immature neural cells and neural precursors were expressed at elevated levels in young postnatal Nfia-/- mice. In contrast, marker genes for differentiated neural cells were downregulated at this stage. In particular, genes relevant for oligodendrocyte differentiation were affected.Our findings suggest that brain development, especially oligodendrocyte maturation, is delayed in Nfia-/- mice during the early postnatal period, which at least partly accounts for their phenotype. The identification of potential NFI-A target genes in our study should help to elucidate NFI-A dependent transcriptional pathways and contribute to enhanced understanding of this period of brain formation, especially with regard to the function of NFI-A.
Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure does not reduce levels of oxidative stress
Authors: Gethin R. Ellis, Angus K. Nightingale, Daniel J. Blackman, Richard A. Anderson, Catherine Mumford, Graham Timmins, Derek Lang, Simon K. Jackson, Michael D. Penney, Malcolm J. Lewis, Michael P. Frenneaux, Jayne Morris‐Thurgood
Journal: European Journal of Heart Failure (2002)
The flagon… with the dragon
Authors: Liam Farrell
Journal: BMJ (2005)

It was more than just a heartsink consultation; it was tedious, nagging, grating, the kind of consultation that whispers the o'erwrought heart and bids it break. “You are in perfect health, Mrs Maguire,” I repeated.

“Are you sure I'm all right?”

“I'm sure.”

“Are you definitely sure?”

“Definitely.”

“Are you absolutely definitely sure?”

“Absolutely.”

“Are you absolutely definitely positively sure?”

“When was the last time someone actually hit you?” …
TIME COURSE OF URINARY ISOPROSTANE EXCRETION AND EFFECT OF ATRIAL NATRIURETIC PEPTIDE ADMINISTRATION ON OXIDATIVE STRESS DURING ACUTE PHASE OF MYOCARDIAL INFARCTION
Authors: Ryosai Nakamura, Hideki Nagoshi, Tetsunori Ishikawa, Haruhito Kumagae, Kouji Kobayashi, Takahiro Sumi, Hironao Iwakiri, Shohei Koyama, Takuroh Imamura, Kazuo Kitamura
Journal: Journal of the American College of Cardiology (2010)
Effect of a Triallelic Functional Polymorphism of the Serotonin-Transporter-Linked Promoter Region on Expression of Serotonin Transporter in the Human Brain
Authors: Ramin V Parsey, Ramin S Hastings, Maria A Oquendo, Xianzhang Hu, David Goldman, Yung-yu Huang, Norman Simpson, Julie Arcement, Yiyun Huang, R Todd Ogden, Ronald L Van Heertum, Victoria Arango, J John Mann
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: The authors examined effects of a triallelic functional polymorphism of the human serotonin-transporter-linked promoter region (5-HTTLPR) on in vivo expression of serotonin transporter in the brain in healthy volunteers and subjects with major depressive disorder. METHOD: Twenty-five medication-free subjects with DSM-IV major depressive disorder during a major depressive episode and 42 healthy volunteers were clinically evaluated and genotyped. Serotonin transporter binding potential (f1Bmax/Kd) was determined by using positron emission tomography with the radiotracer [11C]McN 5652 and metabolite-corrected arterial input functions. RESULTS: There was no difference in serotonin transporter binding potential by genotype in healthy volunteers or in subjects with major depressive disorder. Allelic frequencies did not differ between subjects with major depressive disorder and healthy volunteers. CONCLUSIONS: Associations of the 5-HTTLPR polymorphism to clinical phenotypes appear to be due to developmental effects of 5-HTTLPR on expression and not due to its direct effect on serotonin transporter binding in adulthood.
Resistance to Somatostatin Analogs in Acromegaly
Authors: Annamaria Colao, Renata S. Auriemma, Gaetano Lombardi, Rosario Pivonello
Journal: Endocrine Reviews (2010)

Somatostatin analogs (SA) are widely used in acromegaly, either as first-line or adjuvant treatment after surgery. First-line treatment with these drugs is generally used in the patients with macroadenomas or in those with clinical conditions so severe as to prevent unsafe reactions during anesthesia. Generally, the response to SA takes into account both control of GH and IGF-I excess, with consequent improvement of clinical symptoms directly related to GH and IGF-I excess, and tumor shrinkage. This latter effect is more prominent in the patients treated first-line and bearing large macroadenomas, but it is also observed in patients with microadenomas, even with little clinical implication. Predictors of response are patients' gender, age, initial GH and IGF-I levels, and tumor mass, as well as adequate expression of somatostatin receptor types 2 and 5, those with the highest affinity for octreotide and lanreotide. Only sporadic cases of somatostatin receptor gene mutation or impaired signaling pathways have been described in GH-secreting tumors so far. The response to SA also depends on treatment duration and dosage of the drug used, so that a definition of resistance based on short-term treatments using low doses of long-acting SA is limited. Current data suggest that response to these drugs is better analyzed taking together biochemical and tumoral effects because only the absence of both responses might be considered as a poor response or resistance. This latter evidence seems to occur in 25% of treated patients after 12 months of currently available long-acting SA.
Up-Regulation of <i>NOTCH4</i> Gene Expression in Bipolar Disorder
Authors: Ingrid Dieset, Srdjan Djurovic, Martin Tesli, Sigrun Hope, Morten Mattingsdal, Annika Michelsen, Inge Joa, Tor Ketil Larsen, Ingrid Agartz, Ingrid Melle, Jan Ivar Røssberg, Pål Aukrust, Ole A. Andreassen, Thor Ueland
Journal: American Journal of Psychiatry (2012)

Objective Immunopathogenic mechanisms have been implicated in schizophrenia and bipolar disorder, and genome-wide association studies (GWAS) point to the major histocompatibility complex, a region that contains many immune-related genes. One of the strongest candidate risk genes for schizophrenia and bipolar disorder is the NOTCH4 gene within the major histocompatibility complex. The authors investigated the NOTCH4 gene expression in individuals with bipolar disorder and schizophrenia relative to healthy comparison subjects and identified putative expression quantitative trait loci in and around the NOTCH4 gene. Method The authors measured and compared NOTCH4 mRNA in whole blood in 690 individuals (479 patients and 211 healthy comparison subjects) and adjusted for a range of confounders. The authors also genotyped 20 single-nucleotide polymorphisms (SNPs) and investigated possible associations between expression quantitative trait loci and NOTCH4 expression. Results The authors found a strong association between NOTCH4 expression and bipolar disorder after adjusting for a range of confounders and multiple testing. In addition, seven SNPs within the NOTCH4 gene region were associated with enhanced NOTCH4 mRNA levels. Three of these expression quantitative trait loci were independent (not in linkage disequilibrium). Conclusions The results indicate that the association between NOTCH4 DNA markers and bipolar disorder is related to altered function at the mRNA level, supporting the notion that NOTCH4 pathways are involved in the pathophysiology of bipolar disorder.
Stimulation of Soluble Guanylate Cyclase Activity and Cellular Accumulation of Cyclic Guanosine 3′ ,5′-monophosphate by the Carcinogen 4-Nitroquinoline 1-oxide: Brief Communication 2
Authors: Frederick R. DeRubertis, Patricia A. Craven
Journal: JNCI Journal of the National Cancer Institute (1977)

4-Nitroquinoline 1-oxide (4NQO), a compound that induces tumors in various rat organs, rapidly increased the cellular accumulation of cyclic guanosine 3',5'-monophosphate (cGMP) to peak values fourfold to 13-fold over basal levels in the liver, lung, renal cortex, and gastric and colon mucosa of rats. This action of 4NQO was expressed in the presence or absence of extracellular calcium. When added directly to the broken cell preparations, 4NQO also stimulated guanylate cyclase activity threefold to sixfold over basal levels in the 100,000 X g soluble fractions of each of these tissues. Dicumarol, which blocks the reduction of 4NQO, inhibited 4NQO stimulation of guanylate cyclase and cGMP. Conversely, phenythydrazine, which enhances the reduction of 4NQO, potentiated the actions of 4NQO on guanylate cyclase and cGMP. These results suggested that the activation of the guanylate cyclase-cGMP system may be mediated by reduction products of 4NQO. The activation of the guanylate cyclase system by 4NQO or its derivatives could function in the expression of carcinogenicity.