tbuckley/cabot-search huggingface dataset:
Sex, Age, and Birth Cohort Effects in Colorectal Neoplasms
Authors: Hermann Brenner, Lutz Altenhofen, Michael Hoffmeister
Journal: Annals of Internal Medicine (2010)

Prevalence of advanced colorectal neoplasms increases with age and is higher among men than women. Cross-sectional analyses estimated that men reach an equivalent prevalence at a much younger age than women. However, cross-sectional estimates may be confounded by birth cohort effects.To estimate age and cohort effects in advanced colorectal neoplasms and to adjust risk-advancement periods for men compared with women for birth cohort effects.Age-cohort analyses.German screening colonoscopy program, 2003 to 2007.2 185 153 participants aged 55 to 75 years.Sex- and age-specific prevalence of colorectal cancer (CRC) and advanced neoplasms (CRC or advanced adenoma) were plotted with and without stratification by birth cohort. Risk-advancement periods with 95% CI for men compared with women were estimated from log-binomial regression models with and without cross-sectional analysis adjustment for birth cohort effects.Overall, 17 196 participants (0.8%) had CRC and 152 429 (7.0%) had any advanced neoplasm. Age-specific prevalence was higher in men than in women and in later birth cohorts. The apparent modest increase in prevalence by age in cross-sectional analysis was much steeper after birth cohort effects were controlled for. In cross-sectional analysis, risk-advancement periods (95% CI) for men compared with women were 8.4 years (CI, 7.7 to 9.0 years) and 16.1 years (CI, 15.8 to 16.5 years) for CRC and any advanced neoplasm, respectively, and 3.4 years (CI, 2.6 to 4.3 years) and 6.9 years (CI, 6.4 to 7.4 years) after controlling for birth cohort effects.Information on covariates that could explain cohort effects was lacking.In this population, strong cohort effects reduced age gradients in advanced colorectal neoplasms and inflated risk-advancement periods for men compared with women, but major risk advancement persisted, even after birth cohort effects were controlled for.None.
Detection and functional studies of p60-65 (Tac antigen) on activated human B cells.
Authors: L K Jung, T Hara, S M Fu
Journal: The Journal of Experimental Medicine (1984)

A monoclonal antibody, AT-1, is shown to precipitate a p60-65 molecule identical to the Tac antigen. With AT-1, the expression of IL-2 receptors by normal activated human B cells from peripheral blood and tonsils is documented by biosynthetic and immunofluorescence studies. AT-1 precipitated a p60-65 protein from [35S]methionine-labeled activated B cells, similar to that from activated T cells. The interleukin 2 (IL-2) receptor appeared shortly after activation with anti-IgM and B cell-stimulatory factor(s). Its expression reached its peak at 60-72 h with approximately 50% of the B blasts stained by AT-1. Other modes of activation of B cells, by T cell-independent, formalin-treated staphylococci and Epstein-Barr virus, and by T cell-dependent pokeweed mitogen, also induced IL-2 receptor expression. The functional significance of this finding was investigated using recombinant IL-2 (rIL-2). While rIL-2 did not induce resting B cells to proliferate in the presence of anti-IgM, it induced activated B cells to proliferate in the absence of other factors. On the other hand, rIL-2 did not induce the differentiation of these activated B lymphocytes. These data suggest that IL-2 may play a significant role in B cell activation.
Augmentation of organ-associated natural killer activity by biological response modifiers. Isolation and characterization of large granular lymphocytes from the liver.
Authors: R H Wiltrout, B J Mathieson, J E Talmadge, C W Reynolds, S R Zhang, R B Herberman, J R Ortaldo
Journal: The Journal of Experimental Medicine (1984)

Natural killer (NK) activity in the rat and human has been attributed to cells having the morphology of large granular lymphocytes (LGL). However, this association has been less clear in the mouse, largely because of difficulties in obtaining highly enriched populations of LGL from normal spleen and blood. We have previously observed that the administration of the biological response modifier (BRM) maleic anhydride divinyl ether (MVE-2) strongly augmented NK activity in lung and liver, and the augmented NK activity coincided with increased resistance to the formation of experimental metastases in these organs. The degree of NK augmentation was most striking in the liver, an unexpected and previously unreported observation. In the present study, both MVE-2 or Corynebacterium parvum induced a dramatic augmentation of liver NK activity, which reached maximum levels 3-5 d after treatment. This augmentation of NK activity in the liver coincided with a large increase in the number of lymphoid cells with the morphological characteristics of LGL that could be isolated from enzymatically digested suspensions of perfused liver. The yield of LGL per liver following BRM treatment corresponded to a 10-50-fold increase as compared to normal mice. LGL were purified from these enzymatically digested suspensions of perfused liver by depletion of adherent cells on nylon wool columns and subsequent enrichment for low-density lymphoid cells by fractionation on Percoll density gradients. The enrichment of LGL correlated with greatly increased NK activity against YAC-1. Conversely, the higher-density fractions were depleted of both LGL and NK activity. This increase in NK activity in the liver was suppressed by in vivo treatment with anti-asialo GM1 (asGM1) serum. This treatment also resulted in a corresponding reduction in both the total number and percentage of LGL. By flow cytometry analysis, the phenotype of the majority of these highly cytolytic LGL isolated from the livers of BRM-treated mice were asGM1+, Thy-1+, Ly-5+, Qa-5+, Mac-1+, and Gma-1+, whereas these LGL were Ly-1-, Lyt-2-, L3T4-, and surface Ig-. We conclude that the livers of BRM-treated mice can provide a rich source of highly active mouse LGL that could be used for further characterization of this lymphocyte subset. Further, these studies imply a potential for BRM therapy of neoplastic or viral diseases through augmentation of organ-associated immune responses.
Factors Affecting Progression of Renal Failure in Patients With Type 2 Diabetes
Authors: Hideki Ueda, Eiji Ishimura, Tetsuo Shoji, Masanori Emoto, Tomoaki Morioka, Naoki Matsumoto, Shinya Fukumoto, Takami Miki, Masaaki Inaba, Yoshiki Nishizawa
Journal: Diabetes Care (2003)

OBJECTIVE—Hyperglycemia and hypertension are known to be risk factors for the development of proteinuria in patients with diabetes. Little is known, however, about predictors of progression of renal failure in diabetic patients. RESEARCH DESIGN AND METHODS—We investigated factors affecting progression of renal failure by measuring the doubling of serum creatinine (s-Cr) as an end point in a cohort of 85 type 2 diabetic patients with chronic renal insufficiency/failure (s-Cr &amp;gt;1.5 and &amp;lt;3.7 mg/dl, 61 ± 11 years old, 51 men and 34 women, mean s-Cr 2.3 ± 0.6 mg/dl). RESULTS—The survey period (mean ± SD) was 14.2 ± 10.8 months. The cumulative incidence of the end point in patients with insulin therapy (n = 41) was significantly lower than that in patients without it (n = 44) (P = 0.0022, P values by log-rank test). Multivariate Cox analysis revealed insulin therapy (hazard ratio [HR] 0.435, 95% CI 0.252–0.750, P = 0.0027), serum albumin (0.484, 284–0.823, P = 0.0074), mean blood pressure (1.023, 1.004–1.043, P = 0.017), and hemoglobin (0.841, 0.728–0.972, P = 0.0194) to be independent and significant predictors of progression to renal failure, whereas HbA1c or serum cholesterol were not. CONCLUSION—In type 2 diabetic patients with renal failure, hypoalbuminemia, anemia, higher mean blood pressure, and lack of use of insulin predict rapid progression of renal failure, but HbA1c does not, and insulin therapy may be possibly an indicator of the delay in progression of renal failure.
Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome
Authors: Laurent Papazian, Jean-Marie Forel, Arnaud Gacouin, Christine Penot-Ragon, Gilles Perrin, Anderson Loundou, Samir Jaber, Jean-Michel Arnal, Didier Perez, Jean-Marie Seghboyan, Jean-Michel Constantin, Pierre Courant, Jean-Yves Lefrant, Claude Guérin, Gwenaël Prat, Sophie Morange, Antoine Roch
Journal: New England Journal of Medicine (2010)

In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS.
Opening Up to Precompetitive Collaboration
Authors: Jill S. Altshuler, Erin Balogh, Anna D. Barker, Stephen L. Eck, Stephen H. Friend, Geoffrey S. Ginsburg, Roy S. Herbst, Sharyl J. Nass, Christopher M. Streeter, John A. Wagner
Journal: Science Translational Medicine (2010)

In order to enhance biomedical research and development efficiency and innovation, nontraditional research collaborations have emerged that feature the sharing of information, resources, and capabilities. Although many of these so-called precompetitive collaborations are in the field of oncology, the lessons they offer are broadly applicable to other subfields of translational medicine.
Damage to the nasopharyngeal mucosa induced by current levels of urban air pollution: a field study in lambs
Authors: M Gulisano, S Marceddu, A Barbaro, A Pacini, E Buiatti, A Martini, P Pacini
Journal: European Respiratory Journal (1997)

This study concerns the effects of urban air pollution on the nasopharyngeal epithelium, with the aim of evaluating the possible harmful activity of levels of atmospheric pollution which are not currently considered to be dangerous. Over a 3 month period, 10 lambs kept in a zone characterized by numerous vehicles were sacrificed at regular intervals, and their nasopharyngeal mucosa was examined by scanning electron microscopy and image analysis. Two lambs kept in a rural area were used as controls. The local levels of some airborne contaminants (NO(x), NO2, NO, SO2, CO and particulate matter with aerodynamic diameter &lt; or =10 microm (PM10)) were monitored throughout the experiment. The urban air had an irritating effect, inducing hypersecretion of mucus and morphological damage to the ciliated epithelium. These alterations increased with the duration of exposure to urban air and with increasing pollution levels, although the levels remained below current legal levels. We conclude that the harmful effects of airborne contaminants are probably underestimated. Moreover, physicochemical evaluation of pollution parameters should be complemented by morphological study of upper respiratory epithelium in exposed animals, since this mucosa is a sensitive target for irritating agents.
Loss of angiotensin-II receptors in portal hypertensive rabbits
Authors: James V. Sitzmann, Yuping Wu, Greti Acuilera, Paul A. Cahill, R. Cartland Burns
Journal: Hepatology (1995)

Decreased splanchnic vascular response to exogenous angiotensin-II (A-II) infusion in portal hypertension has recently been documented. A-II receptor density and binding affinity in the mesenteric artery, portal vein, and adrenal gland of normal and portal hypertensive rabbits were studied. Portal hypertension was induced by partial portal vein ligation 3 weeks before study. There were no significant differences in serum concentrations of sodium, potassium, A-II, serum osmolality, or hematocrit between normal and portal hypertensive rabbits. The portal hypertensive portal vein exhibited a 60% fall in A-II receptor number from 65.1 +/- 0.3 fmol/mg in normal to 27.0 +/- 8 fmol/mg (P < .05) in portal hypertension. A significant decrease in receptor number occurred in the portal hypertensive mesenteric artery, 224 +/- 39 fmol/mg compared with 345 +/- 45 fmol/mg in normal rabbits, and in the adrenal cortex 6.8 +/- 1.3 pmol/mg compared with 12.1 +/- 2.5 pmol/mg in normal controls (P < .05). No significant difference in A-II receptor affinity was observed in tissues studied between normal and portal hypertensive rabbits. Autoradiographic study on A-II receptors was consistent with data from membrane binding assays. Receptor subtype analysis showed exclusive type I receptor binding in the mesenteric artery and portal vein. We conclude there is a global reduction in the A-II receptor number in portal hypertension that may mediate much of the decreased response to A-II seen in this disorder. This loss of the A-II receptor may partially explain hemodynamic derangements peculiar to portal hypertension.
Reduction of Nocturnal Awakenings With Mometasone Furoate Administered Via Dry Powder Inhaler in Children With Persistent Asthma Previously Receiving Other Inhaled Corticosteroids
Authors: W.E. Berger, M. Noonan, A. Teper, J. Moreno-Cantu, P. Stryszak, E.O. Meltzer
Journal: Journal of Allergy and Clinical Immunology (2011)
Sleep Complaints as Early Predictors of Posttraumatic Stress Disorder: A 1-Year Prospective Study of Injured Survivors of Motor Vehicle Accidents
Authors: Danny Koren, Isaac Arnon, Peretz Lavie, Ehud Klein
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Disturbed sleep is a common complaint among patients with posttraumatic stress disorder (PTSD) that appears in the reexperiencing and hyperarousal symptom clusters in DSM-IV. The causal relationship between sleep complaints and PTSD is unclear. METHOD: Self-reported insomnia and excessive daytime sleepiness were assessed in 102 victims of motor vehicle accidents and 19 comparison subjects 1 week and 1, 3, 6, and 12 months after the trauma. At 12 months the Structured Clinical Interview for DSM-III-R was administered to determine diagnoses of PTSD. RESULTS: Twenty-six of the accident victims but none of the comparison subjects met the criteria for PTSD. Logistic regression models indicated that sleep complaints from 1 month on were significant in predicting PTSD at 1 year. CONCLUSIONS: These results suggest that on the basis of sleep complaints as early as 1 month after the trauma, it is possible to detect subjects who will later develop chronic PTSD.
Effects of Diet and Sodium Intake on Blood Pressure: Subgroup Analysis of the DASH-Sodium Trial
Authors: William M. Vollmer, Frank M. Sacks, Jamy Ard, Lawrence J. Appel, George A. Bray, Denise G. Simons-Morton, Paul R. Conlin, Laura P. Svetkey, Thomas P. Erlinger, Thomas J. Moore, Njeri Karanja
Journal: Annals of Internal Medicine (2001)

Background: Initial findings from the Dietary Approaches to Stop Hypertension (DASH)-Sodium Trial demonstrated that reduction of sodium intake in two different diets decreased blood pressure in participants with and without hypertension. Objective: To determine effects on blood pressure of reduced sodium intake and the DASH diet in additional subgroups. Design: Randomized feeding study. Setting: Four clinical centers and a coordinating center. Participants: 412 adults with untreated systolic blood pressure of 120 to 160 mm Hg and diastolic blood pressure of 80 to 95 mm Hg. Intervention: Participants followed the DASH diet or a control (typical U.S.) diet for three consecutive 30-day feeding periods, during which sodium intake (50, 100, and 150 mmol/d at 2100 kcal) varied according to a randomly assigned sequence. Body weight was maintained. Measurements: Systolic and diastolic blood pressure. Results: In all subgroups, the DASH diet and reduced sodium intake were each associated with significant decreases in blood pressure; these two factors combined produced the greatest reductions. Among nonhypertensive participants who received the control diet, lower (vs. higher) sodium intake decreased blood pressure by 7.0/3.8 mm Hg in those older than 45 years of age (P < 0.001) and by 3.7/1.5 mm Hg in those 45 years of age or younger (P < 0.05). Conclusion: The DASH diet plus reduced sodium intake is recommended to control blood pressure in diverse subgroups.
DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection
Authors: Todd M. Everson, Genevieve Lyons, Hongmei Zhang, Nelís Soto-Ramírez, Gabrielle A. Lockett, Veeresh K. Patil, Simon K. Merid, Cilla Sӧderhӓll, Erik Melén, John W. Holloway, S. Hasan Arshad, Wilfried Karmaus
Journal: Genome Medicine (2015)

Background: The prevalence of allergic diseases are increasing worldwide, emphasizing the need to elucidate their pathogeneses.The aims of this study were to use a two-stage design to identify DNA methylation levels at cytosine-phosphate-guanine (CpG) sites across the genome associated with atopy and high serum immunoglobulin E (IgE), then to replicate our findings in an independent cohort.Methods: Atopy was assessed via skin prick tests and high serum IgE.Methylation levels were measured from whole blood using the Illumina Infinium HumanMethylation450 BeadChip from 18-year-old women (n = 245) and men (n = 122) in the Isle of Wight birth cohort.After data cleaning and processing, and removing probes with possible single nucleotide polymorphisms, DNA methylation levels from 254,460 CpG sites from the 245 women were subjected to recursive Random Forest feature selection for stage 1.The sites selected from stage 1 were tested in stage 2 for associations with atopy and high IgE levels (>200 kU/L) via logistic regression adjusted for predicted cell-type proportions and sex.Sites significantly associated with atopy in stage 2 underwent replication tests in the independent Swedish birth cohort BAMSE (n = 464). Results:In stage 1, 62 sites were selected, of which 22 were associated with atopy in stage 2 (P-value range 6.5E-9 to 1.4E-5) and 12 associated with high IgE levels (P-value range 1.1E-5 to 7.1E-4) at the Bonferroni adjusted alpha (0.05/62 = 0.0008).Of the 19 available sites, 13 were replicated.Conclusions: We identified 13 novel epigenetic loci associated with atopy and high IgE that could serve as candidate loci for future studies; four were within genes with known roles in the immune response (cg04983687 in the body of ZFPM1, cg18219873 in the 5′UTR of PRG2, cg27469152 in the 3′UTR of EPX, and cg09332506 in the body of COPA).
Maintenance Treatment with Bevacizumab Prolongs Survival in an<i>In vivo</i>Ovarian Cancer Model
Authors: Seiji Mabuchi, Yoshito Terai, Kenichiro Morishige, Akiko Tanabe-Kimura, Hiroshi Sasaki, Masanori Kanemura, Satoshi Tsunetoh, Yoshimichi Tanaka, Masahiro Sakata, Robert A. Burger, Tadashi Kimura, Masahide Ohmichi
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is regarded as a promising therapeutic target. We hypothesized that treatment with bevacizumab, a humanized recombinant anti-VEGF monoclonal antibody, could enhance antitumor response to cisplatin and prolong survival in a murine ovarian cancer model. Experimental Design: We conducted an MTS assay to examine the effect of bevacizumab on proliferation of the VEGF producing human ovarian cancer cell lines in vitro. Next, the antiangiogenic activity of bevacizumab was investigated by in vivo angiogenesis and wound healing assays. We then determined the toxicity and antitumor response of bevacizumab and cisplatin as single agents or in combination in xenograft models of ovarian cancer. Finally, using the same xenograft model, we examined the effect of these regimens, as well as bevacizumab maintenance therapy, on survival. Results: Bevacizumab had no effect on the proliferation of ovarian cancer cells in vitro but significantly inhibited angiogenesis and delayed wound healing in vivo. Bevacizumab inhibited i.p. tumor growth and ascites production in the nu/nu mouse xenograft model and enhanced the therapeutic efficacy of cisplatin. Combination therapy with bevacizumab and cisplatin for 3 weeks was associated with complete disappearance of all macroscopic evidence of disease. Moreover, maintenance treatment with bevacizumab after 3 weeks of induction combination therapy inhibited recurrence and significantly prolonged survival. Conclusions: Bevacizumab has significant antitumor activity not only as a single agent or in combination with cisplatin but may also prolong survival when used as maintenance therapy after a complete response to cisplatin-based chemotherapy.
International Union of Pharmacology. LXVI. Orphan Nuclear Receptors
Authors: Gérard Benoit, Austin Cooney, Vincent Giguere, Holly Ingraham, Mitch Lazar, George Muscat, Thomas Perlmann, Jean-Paul Renaud, John Schwabe, Frances Sladek, Ming-Jer Tsai, Vincent Laudet
Journal: Pharmacological Reviews (2006)

Half of the members of the nuclear receptors superfamily are so-called "orphan" receptors because the identity of their ligand, if any, is unknown. Because of their important biological roles, the study of orphan receptors has attracted much attention recently and has resulted in rapid advances that have helped in the discovery of novel signaling pathways. In this review we present the main features of orphan receptors, discuss the structure of their ligand-binding domains and their biological functions. The paradoxical existence of a pharmacology of orphan receptors, a rapidly growing and innovative field, is highlighted.
Search for the hero inside
Authors: L. Farrell
Journal: BMJ (2010)

“I love the smell of naproxen in the morning,” said the grizzled veteran, surveying the flames and inadvertently disclosing his day job as a pharmaceutical adviser. “Smells of . . . economy—and bendroflumethiazide,” he continued, starting to ramble pointlessly, “That’s cheap and all, just the kind of drug a commie pinko would take. ACEs, they’re more the American way.”

Another fireman came dashing up.

“There are people trapped on the first floor,” he shouted at me enthusiastically. “But you can’t go …
Asymmetric histone modifications between the original and derived loci of human segmental duplications
Authors: Deyou Zheng
Journal: Genome biology (2008)

Sequencing and annotation of several mammalian genomes have revealed that segmental duplications are a common architectural feature of primate genomes; in fact, about 5% of the human genome is composed of large blocks of interspersed segmental duplications. These segmental duplications have been implicated in genomic copy-number variation, gene novelty, and various genomic disorders. However, the molecular processes involved in the evolution and regulation of duplicated sequences remain largely unexplored.In this study, the profile of about 20 histone modifications within human segmental duplications was characterized using high-resolution, genome-wide data derived from a ChIP-Seq study. The analysis demonstrates that derivative loci of segmental duplications often differ significantly from the original with respect to many histone methylations. Further investigation showed that genes are present three times more frequently in the original than in the derivative, whereas pseudogenes exhibit the opposite trend. These asymmetries tend to increase with the age of segmental duplications. The uneven distribution of genes and pseudogenes does not, however, fully account for the asymmetry in the profile of histone modifications.The first systematic analysis of histone modifications between segmental duplications demonstrates that two seemingly 'identical' genomic copies are distinct in their epigenomic properties. Results here suggest that local chromatin environments may be implicated in the discrimination of derived copies of segmental duplications from their originals, leading to a biased pseudogenization of the new duplicates. The data also indicate that further exploration of the interactions between histone modification and sequence degeneration is necessary in order to understand the divergence of duplicated sequences.
733 ANTIVIRAL-THERAPY IN PREGNANCY FOR PREVENTION OF HBV TRANSMISSION: SEVERE POST PARTUM HEPATIC FLARES ARE COMMON AND USUALLY SELF LIMITING
Authors: M. Levy, A. Glass, S. Manoharan, G. Paven, W. Ng, E. Wiseman, S. Locarnini, A. Ayres
Journal: Journal of Hepatology (2011)