tbuckley/cabot-search huggingface dataset:
Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience
Authors: Daryl Tan, Sandra J. Horning, Richard T. Hoppe, Ronald Levy, Saul A. Rosenberg, Bronislava M. Sigal, Roger A. Warnke, Yasodha Natkunam, Summer S. Han, Alan Yuen, Sylvia K. Plevritis, Ranjana H. Advani
Journal: Blood (2013)
microRNA-224 Promotes Cell Proliferation and Tumor Growth in Human Colorectal Cancer by Repressing <i>PHLPP1</i> and <i>PHLPP2</i>
Authors: Wen-Ting Liao, Ting-Ting Li, Zheng-Gen Wang, Shu-Yang Wang, Mei-Rong He, Ya-Ping Ye, Lu Qi, Yan-Mei Cui, Ping Wu, Hong-Li Jiao, Chi Zhang, Yi-Jun Xie, Jun-Xian Wang, Yan-Qing Ding
Journal: Clinical Cancer Research (2013)

To investigate the clinicopathologic significance, role, and mechanism of action of microRNA-224 (miR-224) in colorectal cancer.Real-time PCR was used to quantify miR-224 expression. The association of miR-224 with the clinicopathologic features and survival was evaluated in 110 colorectal cancer patients. The role of miR-224 in colorectal cancer was investigated using in vitro and in vivo assays. Luciferase reporter assays were conducted to confirm target gene associations.miR-224 was overexpressed in colorectal cancer. High-level expression of miR-224 was significantly associated with an aggressive phenotype and poor prognosis. Overexpression of miR-224 promoted colorectal cancer cell proliferation in vitro and tumor growth in vivo. Specifically, miR-224 accelerated the G1-S phase transition through activation of AKT/FOXO3a signaling, downregulation of p21Cip1 and p27Kip1, and upregulation of cyclin D1. Moreover, both PH domain leucine-rich-repeats protein phosphatase 1 (PHLPP1) and PHLPP2, antagonists of PI3K/AKT signaling, were confirmed as bona fide targets of miR-224. miR-224 directly targeted the 3'-untranslated regions of the PHLPP1 and PHLPP2 mRNAs and repressed their expression.This study reveals functional and mechanistic links between miRNA-224 and the tumor suppressors PHLPP1 and PHLPP2 in the pathogenesis of colorectal cancer. miR-224 not only plays important roles in the regulation of cell proliferation and tumor growth in colorectal cancer, but also has potential as a prognostic marker or therapeutic target for colorectal cancer.
Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells
Authors: Daniel R Rines, Maria Gomez-Ferreria, Yingyao Zhou, Paul DeJesus, Seanna Grob, Serge Batalov, Marc Labow, Dieter Huesken, Craig Mickanin, Jonathan Hall, Mischa Reinhardt, Francois Natt, Joerg Lange, David J Sharp, Sumit K Chanda, Jeremy S Caldwell
Journal: Genome biology (2008)

The mitotic spindle is a complex mechanical apparatus required for accurate segregation of sister chromosomes during mitosis. We designed a genetic screen using automated microscopy to discover factors essential for mitotic progression. Using a RNA interference library of 49,164 double-stranded RNAs targeting 23,835 human genes, we performed a loss of function screen to look for small interfering RNAs that arrest cells in metaphase. Here we report the identification of genes that, when suppressed, result in structural defects in the mitotic spindle leading to bent, twisted, monopolar, or multipolar spindles, and cause cell cycle arrest. We further describe a novel analysis methodology for large-scale RNA interference datasets that relies on supervised clustering of these genes based on Gene Ontology, protein families, tissue expression, and protein-protein interactions. This approach was utilized to classify functionally the identified genes in discrete mitotic processes. We confirmed the identity for a subset of these genes and examined more closely their mechanical role in spindle architecture.
Placental protein-1 (plac1) modulates immune tolerance in mammary tumor cells
Authors: Hongyan Yuan, Robert Glazer, Xiaoyi Wang, Lu Jin, James Li, Nairuthya Vijayendra, Venkata Doodala, Spencer Weiss
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Plac1 is an X-linked (Xq26) trophoblast gene expressed at high levels in the placenta, at low levels in the testis, but not in other normal somatic tissues. However, it is re-expressed in several malignancies, including breast, colon, lung, gastric, liver and endometrial cancers
Correlation between interleukin 10 gene promoter region polymorphisms and clinical manifestations in Japanese patients with Sjogren's syndrome
Authors: T Origuchi
Journal: Annals of the Rheumatic Diseases (2003)

Sjogren’s syndrome (SS) is an autoimmune disease characterised by lymphocytic infiltration and glandular tissue dysfunction of exocrine glands such as the salivary and lachrymal glands in genetically susceptible people. Several cytokines, including interleukin 10 (IL10), have been proposed to have a role in the pathogenesis of the disease. Although the major genes involved in susceptibility to SS are within the major histocompatibility complex (MHC) region, several putative non-MHC genetic loci (Ro52,1 IL1,2 IL6,3 Fas/FasL,4 mannose binding lectin,5,6 TAP2,7 and glutathione S-transferase M1 gene8 ) have been proposed as candidate genes. Recently, Hulkkonen et al reported that in Finnish patients the haplotypes formed on the basis of the IL10 gene alleles (at the -1082, -819, and -592 loci) were related to susceptibility to primary SS.9 However, no correlation between extraglandular symptoms …
Glucagon Release Induced by Pancreatic Nerve Stimulation in the Dog
Authors: Errol B. Marliss, Lucien Girardier, Josiane Seydoux, Claes B. Wollheim, Yasunori Kanazawa, Lelio Orci, Albert E. Renold, Daniel Porte
Journal: Journal of Clinical Investigation (1973)

A direct neural role in the regulation of immunoreactive glucagon (IRG) secretion has been investigated during stimulation of mixed autonomic nerves to the pancreas in anesthetized dogs. The responses were evaluated by measurement of blood flow and hormone concentration in the venous effluent from the stimulated region of pancreas. Electrical stimulation of the distal end of the discrete bundles of nerve fibers isolated along the superior pancreaticoduodenal artery was invariably followed by an increase in IRG output. With 10-min periods of nerve stimulation, the integrated response showed that the higher the control glucagon output, the greater was the increment. Atropinization did not influence the response to stimulation. That the preparation behaved in physiologic fashion was confirmed by a fall in IRG output, and a rise in immunoreactive insulin (IRI) output, during hyperglycemia induced by intravenous glucose (0.1 g/kg). The kinetics of this glucose effect on IRG showed characteristics opposite to those of nerve stimulation: the lower the control output, the less the decrement. Furthermore, during the control steady state, blood glucose concentration was tightly correlated with the IRI/IRG molar output ratio, the function relating the two parameters being markedly nonlinear. Injection or primed infusion of glucose diminished the IRG response to simultaneous nerve stimulation. Measurement of IRG was inferred to reflect response of pancreatic glucagon secretion on the basis of the site of sample collection (the superior pancreaticoduodenal vein), the absence of changes in arterial IRG, and similar responses being obtained using an antibody specific for pancreatic glucagon. THESE STUDIES SUPPORT A ROLE FOR THE AUTONOMIC NERVOUS SYSTEM IN THE CONTROL OF GLUCAGON SECRETION: direct nerve stimulation induces glucagon release. Such sympathetic activation may be interpreted as capable of shifting the sensitivity of the A cell to glucose in the direction of higher glycemia for a given glucagon output. The experimental model employed is valid for further studies of regulatory mechanisms of endocrine pancreatic function in vivo.
Predictor of outcome and length of hospital stay in acute viral pneumonia: 2009 H1N1 influenza A experience
Authors: Ashish Jain, Rajesh Chawla, Vikas Sikri, Sudha Kansal
Journal: European Respiratory Journal (2012)

Introduction:- H1N1 Influenza A virus spreads globally causing pneumonia and high mortality.  Aim:- We studied clinical characteristics of patients admitted with influenza pneumonia in a tertiary care hospital of northern India over one year.  Method:- We analyzed 77 patients with H1N1 influenza,confirmed with RT-PCR assay.  Results:-Out of 77 patients,33(43%)were female. Mean age was 41+/-13 years.Thirty eight patients (50%) had at least one comorbidity,Diabetes Mellitus was most frequent. Presenting symptoms were fever in 75 (97%),cough in 67(87%)and dyspnoea in 59 (76%) patients. Mean duration of dyspnoea at presentation was higher in expired group 6 +/-3 Vs 4+/-3 days(P=0.02). Bilateral opacities on chest radiograph seen in 49 (55%) patients. Mean PaO2/FiO2 ratio on admission was 213+/-133 and 175+/- 101 at 24 hours in discharge patients while expired patients it was 141+/-92 and 122+/- 65 respectively. Mean PaCo2 was higher in expired group 55+/-27 Vs 37 +/- 11 (P=0.002). Forty five patients (59 %) had one or more organ failure. Respiratory Failure was commonest (n=43, 56 %) requiring Invasive ventilation in 13(17%) patients and Non invasive ventilator in 23(30%) patients. Overall mortality was 13% (n=10). PaCo2 on admission (odds ratio,1.093; confidence interval, 1.133 to 1.193; P=0.044)and number of organ failure(odds ratio,8.089; confidence interval,1.133 to 57.77;P=0.037)were identified as independent risk factors for in hospital mortality.  Conclusion:-Factors associated with poor outcome in acute viral pneumonia are long duration of dyspnoea, bilateral pneumonia, low PaO2/FiO2 ratio on admission and 24 hours later, high PaCo2 & number of organ failure.
Ileal excretion and bacterial modification of bile acids and cholesterol in patients with continent ileostomy.
Authors: R M Kay, Z Cohen, K P Siu, C N Petrunka, S M Strasberg
Journal: Gut (1980)

Bile acid (acidic sterol) and neutral steroid excretion were determined in 15 patients, five with conventional ileostomy, five with continent ileostomy, and five with continent ileostomy and an ileal resection. Acidic sterol losses were normal in conventional ileostomy patients and not significantly increased in those with continent ileostomy alone. Bile acid excretion rates were significantly increased in patients with a continent ileostomy and an ileal resection. Neutral steroid excretion was similar in all groups and not different from normal. Deoxycholic acid was not detected in ileal effluent of patients with conventional ileostomy and less than 2% of neutral steroid excreted was in the form of bacterial metabolites of cholesterol. The same was true of six of the 10 patients with continent ileostomies; in the other four patients at least 10% of acidic or neutral steroids were excreted as secondary bile acids or as a coprostanol. Modification of steroids was not related to ileal resection. Continent ileostomy was associated with a significant increase in percentage water content and a reduction in the pH of ileal effluent.
Protein-protein interaction networks: probing disease mechanisms using model systems
Authors: Uros Kuzmanov, Andrew Emili
Journal: Genome Medicine (2013)

Protein-protein interactions (PPIs) and multi-protein complexes perform central roles in the cellular systems of all living organisms. In humans, disruptions of the normal patterns of PPIs and protein complexes can be causative or indicative of a disease state. Recent developments in the biological applications of mass spectrometry (MS)-based proteomics have expanded the horizon for the application of systematic large-scale mapping of physical interactions to probe disease mechanisms. In this review, we examine the application of MS-based approaches for the experimental analysis of PPI networks and protein complexes, focusing on the different model systems (including human cells) used to study the molecular basis of common diseases such as cancer, cardiomyopathies, diabetes, microbial infections, and genetic and neurodegenerative disorders.
Oral retinoic acid as therapy for erythrokeratoderma variabilis*
Authors: A. R. WATEREN, R. H. CORMANE
Journal: British Journal of Dermatology (1977)

Oral retinoic acid successfully and rapidly helped two patients with erythrokeratoderma variabilis. Treatment had to be maintained to prevent recurrence and no side effects have been observed so far.
New insights into epididymal biology and function
Authors: G. A. Cornwall
Journal: Human Reproduction Update (2008)

The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. This review focuses on recent progress in our understanding of epididymal function including its development, role of the luminal microenvironment in sperm maturation, regulation and novel mechanisms the epididymis utilizes to carry out some of its functions. A systematic search of Pubmed was carried out using the search term 'epididymis'. Articles that were published in the English language until the end of August 2008 and that focused on the specific topics described above were included. Additional papers cited in the primary reference were also included. While the majority of these findings were the result of studies in animal models, recent studies in the human epididymis are also presented including gene profiling studies to examine regionalized expression in normal epididymides as well as in those from vasectomized patients. Significant progress has been made in our understanding of epididymal function providing new insights that ultimately could improve human health. The data also indicate that the human epididymis plays an important role in sperm maturation but has unique properties compared with animal models.
Conversion of xanthine dehydrogenase into xanthine oxidase in rat liver and plasma at the onset of reperfusion after ischemia
Authors: Arnold Kooij, Henry J. Schiller, Martin Schijns, Cornelis J. F. Van Noorden, Wilma M. Frederiks
Journal: Hepatology (1994)

The aim of this study was to test whether conversion of xanthine dehydrogenase into xanthine oxidase as induced by fasting, ischemia of the liver or both is an in vivo process or only occurs in vitro in homogenates. For this purpose, the conversion rate of xanthine dehydrogenase into xanthine oxidase was studied in liver homogenates obtained from rats after normal feeding or 24 hr of fasting followed or not by 2 hr of ischemia of the liver. In fed rats, the conversion rate of xanthine dehydrogenase into xanthine oxidase was studied as well in liver homogenates after different periods of reperfusion after 2 hr of ischemia. Homogenization was carried out under strictly controlled conditions, after which the supernatants were incubated at 37 degrees C in buffer for 0 to 5 hr. Enzyme activities were assayed spectrophotometrically by measuring urate production at 295 nm. Conversion started only after 2 to 3 hr of incubation of supernatants of control fed livers, whereas conversion started immediately after 24 hr of fasting. The percentage oxidase activity of total xanthine oxidoreductase activity in ischemic livers from fed animals was slightly higher (26.7% +/- 1.7%; p < 0.05) than in control livers (19.3% +/- 1.4%), whereas the percent oxidase activity in ischemic livers from fasted animals (16.7% +/- 1.0%) was not different from that in control animals (16.8% +/- 1.1%). Ischemia for 2 hr caused in vitro a substantial increase in the conversion rate in supernatants of livers of fed and fasted rats as compared with their controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Asthma admissions, smoking bans and administrative databases
Authors: Brian D Kent, Stephen J Lane, Edward D Moloney
Journal: Thorax (2013)

We read with great interest the recent paper by Sims et al, 1 wherein they identified a clinically and statistically significant reduction in admissions with asthma following the implementation of a workplace smoking ban in the UK, independent of prevailing temporal trends and other measureable confounding factors. We welcome this important addition to the evidence base in this area, and endorse the authors’ …
Voltage clamp analysis of the effects of dopamine on the transmembrane ionic currents underlying the action potential of sheep cardiac Purkinje fibers.
Authors: J M Gelles, R S Aronson
Journal: Circulation Research (1977)

Dopamine shifted the voltage-dependence of the slow outward current that underlies spontaneous diastolic depolarization to a more positive voltage range and increased the rate constants of inactivation of this current at voltages negative to -80 mV. Dopamine increased the magnitude of the slow inward current and the delayed outward current. Dopamine had an inconsistent effect on the positive dynamic current and the time-independent potassium current. These effects were consistent with effects on the slope of diastolic depolarization, plateau voltage, and action potential duration and are similar to those of epinephrine. The effects of dopamine on the slow inward current and on the delayed outward current were abolished by verapamil, a slow channel blocker. This finding substantiates that outward potassium currents are modulated by intracellular calcium.
Fruit and Vegetable Intake and Risk of Breast Cancer by Hormone Receptor Status
Authors: Seungyoun Jung, Donna Spiegelman, Laura Baglietto, Leslie Bernstein, Deborah A. Boggs, Piet A. van den Brandt, Julie E. Buring, James R. Cerhan, Mia M. Gaudet, Graham G. Giles, Gary Goodman, Niclas Hakansson, Susan E. Hankinson, Kathy Helzlsouer, Pamela L. Horn-Ross, Manami Inoue, Vittorio Krogh, Marie Lof, Marjorie L. McCullough, Anthony B. Miller, Marian L. Neuhouser, Julie R. Palmer, Yikyung Park, Kim Robien, Thomas E. Rohan, Stephanie Scarmo, Catherine Schairer, Leo J. Schouten, James M. Shikany, Sabina Sieri, Schoichiro Tsugane, Kala Visvanathan, Elisabete Weiderpass, Walter C. Willett, Alicja Wolk, Anne Zeleniuch-Jacquotte, Shumin M. Zhang, Xuehong Zhang, Regina G. Ziegler, Stephanie A. Smith-Warner
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundEstrogen receptor–negative (ER−) breast cancer has few known or modifiable risk factors. Because ER− tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER− breast cancer.
Genome-wide Analysis of the Emigrant Family of MITEs of Arabidopsis thaliana
Authors: Néstor Santiago, Cristina Herráiz, J. Ramón Goñi, Xavier Messeguer, Josep M. Casacuberta
Journal: Molecular Biology and Evolution (2002)

Miniature inverted-repeat transposable elements (MITEs) are structurally similar to defective class II elements, but their high copy number and the size and sequence conservation of most MITE families suggest that they can be amplified by a replicative mechanism. Here we present a genome-wide analysis of the Emigrant family of MITEs from Arabidopsis thaliana. In order to be able to detect divergent ancient copies, and low copy number subfamilies with a different internal sequence we have developed a computer program to look for Emigrant elements based solely on the terminal inverted-repeat sequence. We have detected 151 Emigrant elements of different subfamilies. Our results show that different bursts of amplification, probably of few active, or master, elements, have occurred at different times during Arabidopsis evolution. The analysis of the insertion sites of the Emigrant elements shows that recently inserted Emigrant elements tend to be located far from open reading frames, whereas more ancient Emigrant subfamilies are preferentially found associated to genes.
STUDIES ON MOUSE LEUKEMIA
Authors: Maurice N. Richter, E. C. MacDowell
Journal: The Journal of Experimental Medicine (1930)

Several lines of lymphatic leukemia in mice, experimentally transmitted by inoculation into hosts of a closely inbred strain, have been established and carried on simultaneously. Among the inoculated mice there were found different types of response, according to the line of leukemia inoculated. The differences consisted mainly in the extent or distribution of lesions. Although the same line did not always show the same distribution of lesions, there was a distinct tendency for the cases in a line to present the same characteristics on successive transfers over a considerable period. A comparison of the frequency of the occurrence of certain lesions in four lines of transmission shows that: 1. Increases in the total leucocyte counts were less common and less marked in Lines A and E than in Lines H and I. In the lines first mentioned, normal counts were relatively frequent. In Line H normal counts were uncommon, and in Line I were not observed. The highest counts were found in Line I. 2. Peritoneal effusion was characteristic of Line A for 43 transfers. It was found in Line E, but for a considerably shorter period and in a smaller proportion of cases; it was rare in Lines H and I. 3. Pleural effusion was frequently found in Lines A and E but rarely in Lines H and I. 4. Infiltration in the liver occurred to a marked degree in all the mice of Lines H and I, but in fewer mice and to a variable degree in Lines A and E. 5. Infiltration in the kidney in Line I was present in 90 per cent of the mice, and was of marked grade. In line H it was present in 67 per cent of the mice (24 per cent of marked grade) but in Lines A and E it was rare. 6. A considerable amount of variability in results occurred in Lines A and E, whereas Lines H and I remained remarkably constant. The lesions characteristic of a line were not necessarily those present in the spontaneous case from which the first transfer of the line was made. As the mice used for inoculation were genetically uniform, the differences between the lines are not due to genetic differences in the hosts, but to differences in the materials inoculated.
Add-On Anti–TGF-β Antibody to ACE Inhibitor Arrests Progressive Diabetic Nephropathy in the Rat
Authors: Ariela Benigni, Carla Zoja, Daniela Corna, Cristina Zatelli, Sara Conti, Marco Campana, Elena Gagliardini, Daniela Rottoli, Cristina Zanchi, Mauro Abbate, Steve Ledbetter, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2003)

Renin-angiotensin system (RAS) inhibitors are effective in reducing renal disease progression in early diabetic nephropathy, but they provide imperfect protection at a later stage. Due to the pivotal role of transforming growth factor-beta (TGF-beta) in the pathogenesis of diabetic kidney disease, this study tested the effect of simultaneously interrupting TGF-beta and angiotensin II on disease progression in diabetic rats with overt nephropathy. Diabetes was induced by streptozotocin injection in uninephrectomized rats. Diabetic rats received murine (1D11) or human (CAT-192) anti-TGF-beta monoclonal antibodies alone or in combination with lisinopril, 13C4 irrelevant murine antibody, saline or lisinopril from month 4 (when animals had proteinuria) to month 8. Normal animals served as controls. Systolic BP increase was controlled by single treatments and even more by the combined therapies. 1D11 and lisinopril kept proteinuria at levels numerically lower than irrelevant antibody and saline, while CAT-192 was ineffective. The addition of either TGF-beta antibody to lisinopril normalized proteinuria. Consistent results were obtained for glomerulosclerosis and tubular damage, which were abrogated by the combined therapy. Interstitial volume expansion and infiltration of lymphocytes/macrophages were limited by 1D11 and lisinopril and further reduced by their combination. The increase of type III collagen in the renal interstitium was partially attenuated by 1D11 and lisinopril while normalized by their combination. It is concluded that anti-TGF-beta antibody when added to a background of chronic angiotensin-converting enzyme (ACE) inhibition fully arrests proteinuria and renal injury of overt diabetic nephropathy, providing a novel route to therapy and remission of disease for diabetic patients who do not respond to RAS inhibition.