tbuckley/cabot-search huggingface dataset:
High Expression of <b> <i>PRL-3</i> </b> Promotes Cancer Cell Motility and Liver Metastasis in Human Colorectal Cancer
Authors: Hirotaka Kato, Shuho Semba, Upik A. Miskad, Yasushi Seo, Masato Kasuga, Hiroshi Yokozaki
Journal: Clinical Cancer Research (2004)

Overexpression of PRL-3 has been implicated in colorectal cancer metastases. We investigated the significance of PRL-3 expression in the progression and development of colorectal cancer.We transfected PRL-3-specific small interfering RNA into human colon cancer DLD-1 cells and analyzed its effect on proliferation, motility, and hepatic colonization. Using an in situ hybridization method, we examined the levels of PRL-3 expression in both primary (177 cases) and metastatic (92 cases) human colorectal cancers and elucidated the relationships with clinicopathological parameters including the incidence of metachronous liver and/or lung metastasis after curative surgery for primary tumor.Transient down-regulation of PRL-3 expression in DLD-1 cells abrogated motility (in vitro) and hepatic colonization (in vivo), but no effect on the proliferation of these cells was observed. In human primary colorectal cancers, the frequency of up-regulated PRL-3 expression in cases with liver (84.4%) or lung (88.9%) metastasis was statistically higher than that in cases without either type of metastasis (liver, 35.9%; lung, 42.3%). In metastatic colorectal cancer lesions, high expression of PRL-3 was frequently detected (liver, 91.3%; lung, 100%). Interestingly, metachronous metastasis was observed more frequently in the cases with high PRL-3 expression (P < 0.0001).These results indicate that PRL-3 expression in colorectal cancers may contribute to the establishment of liver metastasis, particularly at the step in which cancer cells leave the circulation to extravasate into the liver tissue. In addition, PRL-3 is expected to be a promising biomarker for identifying colorectal cancer patients at high risk for distant metastases.
Rapid Evolution of a Pollen-Specific Oleosin-Like Gene Family from Arabidopsis thaliana and Closely Related Species
Authors: Manja Schein, Ziheng Yang, Thomas Mitchell-Olds, Karl J. Schmid
Journal: Molecular Biology and Evolution (2004)

It has been shown in a variety of species that genes expressed in reproductive tissues evolve rapidly, which often appears to be the result of positive Darwinian selection. We investigated the evolution of a family of seven pollen-specific oleosin-like proteins (or oleopollenins) in Arabidopsis thaliana and two closely related species. More than 30 kb of a genomic region that harbors the complete, tandemly repeated oleopollenin cluster were sequenced from Arabidopsis lyrata ssp. lyrata, and Boechera drummondii. A phylogenetic analysis of the complete gene cluster from these three species and from Brassica oleracea confirmed its rapid evolution resulting from gene duplication and gene loss events, numerous amino acid substitutions, and insertions/deletions in the coding sequence. Independent duplications were inferred in the lineages leading to Arabidopsis and to Brassica, and gene loss was inferred in the lineage leading to B. drummondii. Comparisons of the ratio of nonsynonymous (d(N)) and synonymous (d(S)) divergence revealed that the oleopollenins are among the most rapidly evolving proteins currently known from Arabidopsis and that they may evolve under positive Darwinian selection. Reverse transcriptase polymerase chain reaction analysis demonstrated the expression of oleopollenins in flowers of the outcrossing A. lyrata, the selfing B. drummondii, and the apomictic Boechera holboellii, suggesting that oleopollenins play an important role in species with different breeding systems. These results are consistent with a putative function in species recognition, but further analyses of protein function and sequence variation in species with different breeding systems are necessary to reveal the underlying causes for the rapid evolution of oleopollenins.
Efficacy and safety of pegylated (40-kd) interferon α-2a compared with interferon α-2a in noncirrhotic patients with chronic hepatitis C
Authors: Rajender K. Reddy, Teresa L. Wright, Paul J. Pockros, Mitchell Shiffman, Gregory Everson, Robert Reindollar, Michael W. Fried, Preston P. Purdum, Donald Jensen, Coleman Smith, William M. Lee, Thomas D. Boyer, Amy Lin, Simon Pedder, Jean DePamphilis
Journal: Hepatology (2001)

Administration of interferon (IFN) 3 times weekly in patients with chronic hepatitis C (CHC) is associated with low sustained responses, which may be, in part, related to this regimen's inability to maintain IFN concentrations sufficient to suppress viral replication. An enhanced IFN molecule produced by the covalent attachment of a branched 40–kd polyethylene glycol moiety to IFN α–2a (PEG[40kd] IFN α–2a) exhibits sustained absorption, a restricted volume of distribution, and reduced clearance compared with unmodified IFN α–2a. One hundred fifty–nine patients with CHC participated in a randomized, ascending–dose (45 or 90, 180, 270 μg) study comparing PEG(40kd) IFN α–2a administered once weekly with 3 MIU IFN α–2a administered 3 times weekly for 48 weeks to determine the most appropriate PEG(40kd) IFN α–2a dose for subsequent clinical trials. Efficacy was assessed by measuring hepatitis C virus (HCV) RNA following a 24–week treatment–free period. Sustained virological responses for PEG(40kd) IFN α–2a once weekly were 10% (45 μg; not significant), 30% (90 μg; P = .009), 36% (180 μg; P = .0006), and 29% (270 μg; P = .004), compared with 3% for the 3–times–weekly 3–MIU IFN α–2a regimen. The types and frequencies of adverse events and laboratory abnormalities were similar among all groups. In conclusion, once–weekly PEG(40kd) IFN α–2a was associated with a higher number of sustained virological responses compared with IFN α–2a 3 times weekly in patients with CHC, but had a similar safety profile. The 180–μg PEG(40kd) IFN α–2a dose appeared to be the optimal dose based on sustained virological response and its associated side–effect profile.
Racial Disparities in Access to Pediatric Kidney Transplantation Since Share 35
Authors: Sandra Amaral, Rachel E. Patzer, Nancy Kutner, William McClellan
Journal: Journal of the American Society of Nephrology (2012)

Share 35 was enacted in 2005 to shorten transplant wait times and provide high-quality donors to children with ESRD. To investigate the possible effect of this policy on racial disparities in access to pediatric transplantation, we analyzed data from the US Renal Data System before and after Share 35. Among 4766 pediatric patients with incident ESRD, the probability of receiving a deceased-donor kidney transplant increased 46% after Share 35, with Hispanics experiencing the greatest improvements (increases of 81% for Hispanics, 45% for blacks, and 37% for whites). On average, patients received a deceased-donor kidney transplant earlier after Share 35, but this finding varied by race: 63 days earlier for whites, 90 days earlier for blacks, and 201 days earlier for Hispanics. Furthermore, a shift from living- to deceased-donor sources occurred with Share 35 for all races, with a 25% reduction in living donors for whites compared with 48% and 46% reductions for Hispanics and blacks, respectively. In summary, Share 35 seems to have attenuated racial disparities in the time to and probability of children receiving a deceased-donor kidney transplant. These changes coincided with changes in the rates of living-donor sources, which vary by race. Future studies should explore how these changes may impact racial differences in long-term graft outcomes.
Characterization of interleukin 5 receptors on eosinophilic sublines from human promyelocytic leukemia (HL-60) cells.
Authors: G Plaetinck, J Van der Heyden, J Tavernier, I Faché, T Tuypens, S Fischkoff, W Fiers, R Devos
Journal: The Journal of Experimental Medicine (1990)

The T cell product interleukin 5 (IL-5) has been shown to be a key factor in the development and the maturation of the eosinophilic cell lineage. We report here on the detection of human IL-5 receptors on eosinophilic sublines of the promyelocytic leukemia HL-60. Sodium butyrate, which initiates differentiation to mature eosinophils, also induces the appearance of high affinity (Kd 1-5 X 10(-11) M) IL-5 binding sites on these cells. The receptors are specific for IL-5, since binding of radiolabeled ligand can only be inhibited with homologous or murine IL-5 and not by other cytokines. We further show that the receptors are functional, since IL-5 can stimulate the proliferation of these cells. Affinity crosslinking of surface-bound 125I human IL-5 or 35S mouse IL-5 identified two membrane polypeptides of approximately 60 and approximately 130 kD to which IL-5 is closely associated. The presence of granulocyte/macrophage-colony-stimulating factor or tumor necrosis factor during butyrate induction decreased the expression of IL-5 binding sites compared with control cultures. The identification and characterization of human IL-5 receptors on HL-60 sublines should provide new insight into the role of this cytokine in eosinophil differentiation.
Angiotensin-Converting Enzyme-2 (ACE2)—A New Player in the Genesis of Glomerular Injury?
Authors: G.Y. Oudit, A.M. Herzenberg, Z. Kassiri, D. Wong, H. Reich, R. Khokha, M.A. Crackower, P.H. Backx, J.M. Penninger, J.W. Scholey
Journal: Journal of the American Society of Nephrology (2006)

In the good old days, the world of the renin-angiotensin (ANG) system was clear and straightforward. In a first step, the protease renin cleaved the decapeptide ANGI (angiotensin 1-10) from the substrate angiotensinogen. In a second step, the dicarboxypeptidase angiotensin-converting enzyme (ACE)
Helicobacter pylori and upper gastrointestinal symptoms in bronchiectasis
Authors: KW Tsang, WK Lam, E Kwok, KN Chan, WH Hu, GC Ooi, L Zheng, BC Wong, SK Lam
Journal: European Respiratory Journal (1999)

The recently reported increase in seroprevalence of Helicobacter pylori, the causative pathogen in peptic ulceration, in bronchiectasis is unexplained. Therefore, the association of antibodies directed against cytotoxin-associated gene A(CagA), whose expression indicates virulence of H. pylori, and upper gastrointestinal symptoms in patients with stable bronchiectasis and healthy volunteers evaluated. One hundred patients (mean +/- SD age 55.1+/-16.7 yrs) and 94 healthy asymptomatic subjects (54.6+/-7.6 yrs) underwent clinical and physiological assessment and serum levels of anti-H. pylori CagA were determined using standard clinical and enzyme-linked immunosorbent assay techniques. Samples were positive for anti-H. pylori CagA in 11.7% of controls and 24% of bronchiectatic subjects (p = 0.03). There was, however, no association between serum H. pylori CagA immunoglobulin G level and forced expiratory volume in one second (FEV1), forced vital capacity (FVC), sputum volume, respiratory symptoms or upper respiratory gastrointestinal symptoms (p&gt;0.05). Patients who suffered from acid regurgitation or upper abdominal distension had significantly lower FEV1 and FVC (as a percentage of the predicted value) compared to their counterparts. The results of anticytotoxin-associated gene A measurements in this study contrasted with the previous finding that anti-Helicobacter pylori immunoglobulin G correlated with sputum volume. These findings, therefore, suggest that Helicobacter pylori, should it have a pathogenic role in bronchiectasis, could act via noncytotoxin-associated gene A-mediated mechanisms, and, in this context, gastro-oesophageal reflux might be of importance in bronchiectasis.
Peer support among persons with severe mental illnesses: a review of evidence and experience
Authors: LARRY DAVIDSON, CHYRELL BELLAMY, KIMBERLY GUY, REBECCA MILLER
Journal: World Psychiatry (2012)

Peer support is largely considered to represent a recent advance in community mental health, introduced in the 1990s as part of the mental health service user movement. Actually, peer support has its roots in the moral treatment era inaugurated by Pussin and Pinel in France at the end of the 18th century, and has re-emerged at different times throughout the history of psychiatry. In its more recent form, peer support is rapidly expanding in a number of countries and, as a result, has become the focus of considerable research. Thus far, there is evidence that peer staff providing conventional mental health services can be effective in engaging people into care, reducing the use of emergency rooms and hospitals, and reducing substance use among persons with co-occurring substance use disorders. When providing peer support that involves positive self-disclosure, role modeling, and conditional regard, peer staff have also been found to increase participants' sense of hope, control, and ability to effect changes in their lives; increase their self-care, sense of community belonging, and satisfaction with various life domains; and decrease participants' level of depression and psychosis.
Left Ventricular Stiffness Associated with Chronic Pressure and Volume Overloads in Man
Authors: William Grossman, Lambert P. McLaurin, Miltiadis A. Stefadouros
Journal: Circulation Research (1974)

The relative effects of chronic pressure overload and chronic volume overload on left ventricular diastolic chamber stiffness were examined using a combined hemodynamic and ultrasonic technique in 27 patients. The slope of the left ventricular pressure-diameter relation in late diastole was measured and found to be steep in the groups with pressure or volume overload (9.0 ± 1.8 mm Hg/mm for pressure overload, 5.6 ± 0.9 mm Hg/mm for volume overload) compared with a control group (2.2 ± 0.2 mm Hg/mm). When this slope was normalized for either pressure or diameter, chamber stiffness remained high in the pressure-overloaded ventricles but was only slightly increased in the volume-overloaded ventricles compared with control. Ventricular wall thickness was much greater in pressure-overloaded ventricles (15.6 ± 1.0 mm) than it was in normal (9.0 ± 0.4 mm) ventricles but only slightly increased in volume-overloaded ventricles (10.6 ± 0.9 mm). The large increases in both effective and normalized diastolic stiffness indexes associated with chronic pressure overload suggest an increase in intrinsic left ventricular chamber stiffness, possibly related to an increase in wall thickness. In contrast, chronic volume overload results in only slight increases in normalized diastolic stiffness indexes and wall thickness. It is suggested that differences in the pattern of hypertrophy, which result in a significant disparity in ventricular wall thickness between the two conditions, best account for the observed differences in diastolic left ventricular chamber stiffness.
Guided Self-Change for Bulimia Nervosa Incorporating Use of a Self-Care Manual
Authors: Cornelia Thiels, Ulrike Schmidt, Janet Treasure, Rolf Garthe, Nicolas Troop
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The aim of this study was to evaluate the effectiveness of guided self-change for bulimia nervosa. METHOD: Sixty-two patients with DSM-III-R-defined bulimia nervosa were randomly assigned to 1) use of a self-care manual plus eight fortnightly sessions of cognitive behavior therapy (guided self-change) or 2) 16 sessions of weekly cognitive behavior therapy. RESULTS: At the end of treatment and at follow-up an average of 43 weeks after the end of therapy, substantial improvements had been achieved in both groups on the main outcome measures: eating disorder symptoms according to experts' ratings (Eating Disorder Examination subscores on overeating, vomiting, dietary restraint, and shape and weight concerns), self-reports (Bulimic Investigatory Test Edinburgh), and a 5-point severity scale. Also, improvement was seen on the subsidiary outcome measures: the Beck Depression Inventory, the Self-Concept Questionnaire, and knowledge of nutrition, weight, and shape. At follow-up, 71% of the cognitive behavior therapy group had not binged or vomited during the week preceding. In the guided self-change group, 70% had not binged and 61% had not vomited during the week before follow-up. CONCLUSIONS: Guided self-change incorporating use of a self-care manual offers an approach that can be as effective as standard cognitive behavior therapy in the long term and can considerably reduce the amount of therapist contact required. (Am J Psychiatry 1998; 155:947–953)
The influence of the number of follicles on pregnancy rates in intrauterine insemination with ovarian stimulation: a meta-analysis
Authors: M.M.E. van Rumste, I.M. Custers, F. van der Veen, M. van Wely, J.L.H. Evers, B.W.J. Mol
Journal: Human Reproduction Update (2008)

The influence of multifollicular growth on pregnancy rates in subfertile couples undergoing intrauterine insemination (IUI) with controlled ovarian hyperstimulation (COH) remained unclear.Relevant papers were identified by searching MEDLINE, EMBASE and the Cochrane Library. A meta-analysis was performed and Mantel-Haenszel pooled odd ratios (ORs) and risk differences with 99% confidence intervals (CIs) were calculated to express the relation between the number of follicles and pregnancy rates.We included 14 studies reporting on 11 599 cycles. The absolute pregnancy rate was 8.4% for monofollicular and 15% for multifollicular growth. The pooled OR for pregnancy after two follicles as compared with monofollicular growth was 1.6 (99% CI 1.3-2.0), whereas for three and four follicles, this was 2.0 and 2.0, respectively. Compared with monofollicular growth, pregnancy rates increased by 5, 8 and 8% when stimulating two, three and four follicles. The pooled OR for multiple pregnancies after two follicles was 1.7 (99% CI 0.8-3.6), whereas for three and four follicles this was 2.8 and 2.3, respectively. The risk of multiple pregnancies after two, three and four follicles increased by 6, 14 and 10%. The absolute rate of multiple pregnancies was 0.3% after monofollicular and 2.8% after multifollicular growth.Multifollicular growth is associated with increased pregnancy rates in IUI with COH. Since in cycles with three or four follicles the multiple pregnancy rate increased without substantial gain in overall pregnancy rate, IUI with COH should not aim for more than two follicles. One stimulated follicle should be the goal if safety is the primary concern, whereas two follicles may be accepted after careful patient counselling.
Genetic Sensitivity to the Environment: The Case of the Serotonin Transporter Gene and Its Implications for Studying Complex Diseases and Traits
Authors: Avshalom Caspi, Ahmad R Hariri, Andrew Holmes, Rudolf Uher, Terrie E. Moffitt
Journal: American Journal of Psychiatry (2010)

Evidence of marked variability in response among people exposed to the same environmental risk implies that individual differences in genetic susceptibility might be at work. The study of such Gene-by-Environment (GxE) interactions has gained momentum. In this article, the authors review research about one of the most extensive areas of inquiry: variation in the promoter region of the serotonin transporter gene (SLC6A4; also known as 5-HTT) and its contribution to stress sensitivity. Research in this area has both advanced basic science and generated broader lessons for studying complex diseases and traits. The authors evaluate four lines of evidence about the 5-HTT stress-sensitivity hypothesis: 1) observational studies about the serotonin transporter linked polymorphic region (5-HTTLPR), stress sensitivity, and depression in humans; 2) experimental neuroscience studies about the 5-HTTLPR and biological phenotypes relevant to the human stress response; 3) studies of 5-HTT variation and stress sensitivity in nonhuman primates; and 4) studies of stress sensitivity and genetically engineered 5-HTT mutations in rodents. The authors then dispel some misconceptions and offer recommendations for GxE research. The authors discuss how GxE interaction hypotheses can be tested with large and small samples, how GxE research can be carried out before as well as after replicated gene discovery, the uses of GxE research as a tool for gene discovery, the importance of construct validation in evaluating GxE research, and the contribution of GxE research to the public understanding of genetic science.
A Genomic Approach to Human Autoimmune Diseases
Authors: Virginia Pascual, Damien Chaussabel, Jacques Banchereau
Journal: Annual Review of Immunology (2010)

The past decade has seen an explosion in the use of DNA-based microarrays. These techniques permit assessment of RNA abundance on a genome-wide scale. Medical applications emerged in the field of cancer, with studies of both solid tumors and hematological malignancies leading to the development of tests that are now used to personalize therapeutic options. Microarrays have also been used to analyze the blood transcriptome in a wide range of diseases. In human autoimmune diseases, these studies are showing potential for identifying therapeutic targets as well as biomarkers for diagnosis, assessment of disease activity, and response to treatment. More quantitative and sensitive high-throughput RNA profiling methods are starting to be available and will be necessary for transcriptome analyses to become routine tests in the clinical setting. We expect this to crystallize within the coming decade, as these methods become part of the personalized medicine armamentarium.
Double-Blind Comparison of the Continued Use of Antipsychotic Treatment Versus Its Discontinuation in Remitted Manic Patients
Authors: Carlos A. Zarate, Mauricio Tohen
Journal: American Journal of Psychiatry (2004)

The goal of this study was to determine the benefits of the continued use of a typical antipsychotic agent following remission from an acute manic episode.Immediately following remission of a manic episode treated with the combination of a typical antipsychotic (perphenazine) and a mood stabilizer (lithium, carbamazepine, or valproate), 37 patients were randomly assigned to 6 months of double-blind treatment in which in addition to the mood stabilizer they received either continued perphenazine treatment or placebo.Patients randomly assigned to continue perphenazine treatment, relative to those who discontinued it, were more likely to have a shorter time to depressive relapse, discontinue the study, and have increased rates of dysphoria, depressive symptoms, and extrapyramidal symptoms.There were no short-term benefits with the continued use of a typical antipsychotic after achieving remission from an episode of acute mania. In fact, its continued use was associated with detrimental effects.