tbuckley/cabot-search huggingface dataset:
Serum pepsinogens I and II and gastric mucosal histology after partial gastrectomy.
Authors: P Sipponen, I M Samloff, M Saukkonen, K Varis
Journal: Gut (1985)

We determined the effect of postgastrectomy gastritis on serum pepsinogen I and pepsinogen II concentrations in 108 subjects with subtotal gastric resection. Eleven had normal remnant mucosa, 22 had superficial gastritis, and 75 had atrophic gastritis. In the subjects with superficial gastritis, serum pepsinogen I and II concentrations were significantly higher than in those with normal remnant mucosa, but the ratio of pepsinogen I to II did not differ from normal. In atrophic gastritis, serum pepsinogen I concentrations fell with increasing severity of mucosal damage, but pepsinogen II was persistently raised. Consequently, the ratio of pepsinogen I to II in subjects with atrophic gastritis was significantly lower than in those with superficial gastritis or normal remnant mucosa. Discriminant function analysis revealed that the ratio of pepsinogen I to II, in combination with the absolute level of pepsinogen II, had a sensitivity of 80%, a specificity of 73%, and a positive predictive value of 87% for atrophic gastritis in this population. We propose that the parallel increase in serum pepsinogen I and II concentrations in postgastrectomy superficial gastritis is because of an increased rate of endocrine release of both zymogens from the fundic glands, and that the dichotomy in pepsinogen I and II concentrations in postgastrectomy atrophic gastritis results from the loss of fundic glands, which produce both zymogens, and the appearance of metaplastic pyloric glands, which produce only pepsinogen II.
BR22, a 26 kDa thyroid transcription factor‐1 associated protein (TAP26), is expressed in human lung cells
Authors: M-C.W. Yang, B. Wang, J.C. Weissler, L.R. Margraf, Y-S. Yang
Journal: European Respiratory Journal (2003)

The current authors have previously identified BR22, a thyroid transcription factor (TTF)‐1 associated protein 26 (TAP26), which interacts with TTF‐1 to enhance human surfactant protein (SP)‐B promoter activity in transfected 293 cells. However, the expression of TAP26 in the lung cells and its biological relevance to the SP‐B production under physiological conditions were not examined. In this study, endogenous co-immunoprecipitation and in situ immunohistochemical staining techniques were employed to explore the presence of TAP26 and TTF‐1 complex in the lung epithelial cells. The correlation of TAP26, TTF‐1 and SP‐B expression was inspected in H441 cells in the presence of dexamethasone, a known positive effector of the SP‐B promoter. Monoclonal antibody (mAb) against TAP26 can co-immunoprecipitate both TAP26 and TTF‐1 from H441 cells. Using this antibody in in situ staining of human lung sections, the data show that TAP26 is present in the lung alveolar epithelial cells. Reverse transcriptase-polymerase chain reaction and Western blot analyses of type-II cells as well as dexamethasone-treated H441 cells suggest that TAP26 expression is modulated coordinately with SP‐B and TTF‐1 in these cells. In summary, the current study demonstrates that thyroid transcription factor‐1 associated protein 26 is an associated protein of thyroid transcription factor‐1 in the lung alveolar epithelial cells where surfactant protein gene expressions take place in vivo .
Intron Loss and Gain in Drosophila
Authors: Jasmin Coulombe-Huntington, Jacek Majewski
Journal: Molecular Biology and Evolution (2007)

Although introns were first discovered almost 30 years ago, their evolutionary origin remains elusive. In this work, we used multispecies whole-genome alignments to map Drosophila melanogaster introns onto 10 other fully sequenced Drosophila genomes. We were able to find 1,944 sites where an intron was missing in one or more species. We show that for most (>80%) of these cases, there is no leftover intronic sequence or any missing exonic sequence, indicating exact intron loss or gain events. We used parsimony to classify these differences as 1,754 intron loss events and 213 gain events. We show that lost and gained introns are significantly shorter than average and flanked by longer than average exons. They also display quite distinct phase distributions and show greater than average similarity between the 5′ splice site and its 3′ partner splice site. Introns that have been lost in one or more species evolve faster than other introns, occur in slowly evolving genes, and are found adjacent to each other more often than would be expected for independent single losses. Our results support the cDNA recombination mechanism of intron loss, suggest that selective pressures affect site-specific loss rates, and show conclusively that intron gain has occurred within the Drosophila lineage, solidifying the "introns-middle" hypothesis and providing some hints about the gain mechanism.
Diabetes and Associated Risk Factors Among Asian American Subgroups in New York City
Authors: Nadia S. Islam, Laura C. Wyatt, Smiti B. Kapadia, Mariano J. Rey, Chau Trinh-Shevrin, Simona C. Kwon
Journal: Diabetes Care (2012)

The diabetes burden is disproportionately experienced by minorities in the U.S., particularly diverse Asian American subgroups. National age-adjusted diabetes rates range from 4.0% among Koreans to 14.2% among Asian Indians (1). In New York City (NYC), foreign-born South Asians have an age-adjusted diabetes prevalence nearly twice as high as foreign-born “other Asians” (13.6 vs. 7.4%) (2). Existing studies on Asian Americans are hampered by a lack of generalizability or inability to distinguish between Asian subgroups (2,3). Our study builds upon the existing literature by examining diabetes prevalence rates and risk factors among three of the largest Asian American subgroups in NYC.

The current analysis uses combined data from three waves of the Racial and Ethnic Approaches to Community Health across the U.S. (REACH U.S.) Risk Factor Survey (2009–2011). An address-based sampling frame method was used to oversample Asian Americans while reducing the bias of traditional random-digit dialing; further details on methodology are described elsewhere (4). …
Pulmonary receptor for advanced glycation end-products promotes asthma pathogenesis through IL-33 and accumulation of group 2 innate lymphoid cells
Authors: Elizabeth A. Oczypok, Pavle S. Milutinovic, John F. Alcorn, Anupriya Khare, Lauren T. Crum, Michelle L. Manni, Michael W. Epperly, Adriane M. Pawluk, Anuradha Ray, Tim D. Oury
Journal: Journal of Allergy and Clinical Immunology (2015)
Bronchiolitis obliterans syndrome in lung transplant recipients is associated with increased neutrophil activity and decreased antioxidant status in the lung
Authors: GC Riise, A Williams, C Kjellstrom, H Schersten, BA Andersson, FJ Kelly
Journal: European Respiratory Journal (1998)

Long-term survival of lung transplant recipients is limited by the advent of obliterative bronchiolitis and irreversible airways obstruction, e.g. bronchiolitis obliterans syndrome (BOS). This study investigated whether inflammatory cells and their activation markers were increased in bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) from patients with BOS. Levels of antioxidants in BAL fluid were also assessed. BAL fluid and TBB from six single-lung, two bilateral-lung, and five heart-lung transplanted patients with diagnosis of BOS were compared with 13 transplant recipients without BOS. BAL fluid levels of myeloperoxidase (MPO), eosinophil cationic protein (ECP) and interleukin (IL)-8 were used as markers for the activation and attraction of neutrophils and eosinophils, respectively. Immunohistochemical staining of TBB with monoclonal antibodies to MPO and ECP (EG2) was performed. Significantly increased BAL percentages of neutrophils and levels of MPO were found in patients with BOS. The findings correlated well with the degree of monoclonal staining for MPO in TBB. BAL levels of ECP and IL-8 were significantly increased in BOS patients. BAL concentrations of the water-soluble antioxidants ascorbate, urate and glutathione were generally lower in BOS patients. The results indicate that neutrophil infiltration and activation, as well as oxidative stress, may play a role in the development and/or progression of bronchiolitis obliterans syndrome. Markers for neutrophil activation could have a potential role in monitoring disease activity in patients with this syndrome.
Systematic Review of Psychological Therapies for Cancer Patients: Overview and Recommendations for Future Research
Authors: Sallie Anne Newell, Rob William Sanson-Fisher, Nina Johanna Savolainen
Journal: JNCI Journal of the National Cancer Institute (2002)

Many cancer patients use psychological therapies because they expect them to cure their cancer or to improve their recovery. Despite these high expectations, both patients and oncologists report being moderately to very satisfied with the results of psychological therapies. Previous reviews of the literature have concluded that psychological therapies may help cancer patients in various ways, ranging from reducing the side effects of cancer treatments to improving patients' immune function and longevity. However, because those reviews lacked methodologic rigor, we critically and systematically reviewed all identifiable publications about psychological therapies used by cancer patients to provide an objective and scientific evaluation of nontraditional therapies. We identified 627 relevant papers that reported on 329 intervention trials by searching MEDLINE™, Healthplan™, Psychlit™, and Allied and Complementary Medicine™ databases and in the bibliographies of the papers identified. Despite increased use of randomized, controlled trial designs over time, the methodologic quality of the intervention trials, on 10 internal validity indicators, was generally suboptimal, with only one trial achieving a quality rating of “good” for its methodology. Using effectiveness results from 34 trials with psychosocial outcomes, 28 trials with side effect outcomes, 10 trials with conditioned side-effect outcomes, and 10 trials with survival or immune outcomes, we make only tentative recommendations about the effectiveness of psychological therapies for improving cancer patients' outcomes. Nevertheless, by exploring the relative effectiveness of the different intervention strategies for each outcome and follow-up period, we suggest the specific therapies that should be considered for further investigation. In addition, we suggest how future trials can maximize their internal validity by describing the minimal reporting standards that should be required in this field.
Defect in Microvascular Adaptation to Chronic Changes in Blood Flow in Mice Lacking the Gene Encoding for Dystrophin
Authors: Laurent Loufrani, Bernard I. Levy, Daniel Henrion
Journal: Circulation Research (2002)

Dystrophin has a key role in striated muscle mechanotransduction. In mice lacking the gene encoding for dystrophin (mdx mice), the absence of dystrophin and several other proteins of the dystrophin-glycoprotein complex induces a defect in flow (shear stress)–mediated NO-dependent dilation (FMD). Because the endothelium is essential for the adaptation of arteries to chronic changes in blood flow, the long-term consequences of this vascular deficiency might affect flow-induced vascular remodeling. Thus, we submitted mouse mesenteric resistance arteries to chronic changes in flow by alternatively ligating arteries. Arteries were thus submitted to high flow (HF), low flow (LF), or normal flow. After 2 weeks, arteries were studied in vitro in an arteriograph. Increases in diameter (from 174±10 to 210±15 μm, pressure 75 mm Hg) found in HF arteries were not significant in mdx mice. Arterial diameters in LF arteries decreased similarly in control and mdx mice. FMD increased in HF arteries and decreased in LF arteries. FMD was not increased in HF arteries in mdx mice. NO-dependent FMD and NO synthase expression increased in the HF arteries of control mice but not in those of mdx mice. Dilatory and contractile tone, depending on the smooth muscle, was unaffected in HF arteries but decreased in LF arteries of both strains. We conclude that resistance arteries of mdx mice do not adapt properly to chronic changes in flow, inasmuch as the increases in diameter, endothelial NO synthase expression, and FMD did not occur in mdx mice submitted to HF for 2 weeks. This study suggests that blood flow regulation might be disturbed in dystrophin-related myopathies, possibly increasing organ damage.
Phenylbutyrate interferes with the Fanconi anemia and BRCA pathway and sensitizes head and neck cancer cells to cisplatin
Authors: Kyunghee Burkitt, Mats Ljungman
Journal: Molecular Cancer (2008)

Cisplatin has been widely used to treat head and neck cancer. One of the clinical limitations with this treatment, however, is that tumors that are initially responsive to cisplatin later acquire resistance. We have recently shown that a subset of head and neck cancer cell lines has a defective Fanconi anemia DNA damage response pathway and this defect correlates to cisplatin sensitivity. We have also shown that the histone deacetylase inhibitor phenylbutyrate sensitize human cells to cisplatin. In this study we explored whether phenylbutyrate may sensitize head and neck cancer cells by interfering with the Fanconi anemia pathway. We found that the phenylbutyrate sensitizes head and neck cancer cell lines to cisplatin. This sensitization by phenylbutyrate correlated to a significant decrease in the formation of cisplatin-induced FANCD2 nuclear foci, which is a functional read out of the Fanconi anemia and BRCA (FA/BRCA) pathway. This abrogation of the FA/BRCA pathway by phenylbutyrate was not due to loss of FANCD2 monoubiquitylation but rather correlated to a phenylbutyrate-mediated reduction in the expression of the BRCA1 protein. Furthermore, we found that cancer cells defective in the FA pathway were also sensitized to cisplatin by phenylbutyrate suggesting that phenylbutyrate targets additional pathways. The results from this study suggest that phenylbutyrate may have therapeutic utility as a cisplatin sensitizer in head and neck cancer by inhibiting the FA/BRCA pathway through the down regulation of BRCA1 as well as by an FA/BRCA-independent mechanism.
Erythropoietin: Pharmacology, Biogenesis and Control of Production
Authors: James W. Fisher
Journal: Pharmacological Reviews (1972)

The purpose of this review has been to describe the pharmacological actions of erythropoietin and its role in the control of erythropoiesis. It includes: a historical introduction on the discovery of the humoral control of erythropoiesis; techniques used for the assay and standardization of erythropoietin; purification and physicochemical characterization of erythropoietin; renal and extrarenal sites of production of erythropoietin; the biogenesis of erythropoietin as it pertains to the renal erythropoietic factor (erythrogenin); and a schematic model for the renal control of erythropoietin production. Pharmacological agents included in this review which are known to increase erythropoietin production are androgens, pituitary ACTH (through an action on the release of glucocorticoids from the adrenal), angiotensin, norepinephrine, 5-hydroxytryptamine (5-HT), vasopressin, prostaglandins, dibutyryl cyclic 3’, 5’-AMP and cobalt. The pharmacological agents which depress erythropoietin production are the diuretic drugs, such as mercurials, triamterene, benzydroflumethiazide, as well as chlorambudil, thio-TEPA, actinomycin D, and ionizing radiation. Other areas in the review include: the nervous system and carotid body influences on erythropoiesis; physiological and pathological inhibitors of erythropoietin and erythropoiesis; the mechanisms and sites of action of erythropoietin on the erythron; and clinical anemias and polycythemias associated with erythropoietin secretion. The recent reports on the complete isolation, purification and characterization of erythropoietin offer hope that sufficient amounts of this glycoprotein-hormone will be available in the near future for the treatment of some of the erythropoietin deficiency anemias.
COP1, the Negative Regulator of p53, Is Overexpressed in Breast and Ovarian Adenocarcinomas
Authors: David Dornan, Sheila Bheddah, Kim Newton, William Ince, Gretchen D. Frantz, Patrick Dowd, Hartmut Koeppen, Vishva M. Dixit, Dorothy M. French
Journal: Cancer Research (2004)

The tumor suppressor protein p53 plays a central role in protecting normal cells from undergoing transformation. Thus, it is fitting that cancer cells selectively dampen the p53 response to gain a selective growth advantage. In fact, the p53 gene is the most commonly mutated tumor suppressor gene in human cancers, and if the gene is not mutated, then other components of the p53 pathways are skewed to dampen the p53 response to stress. We recently identified COP1 as a novel and critical negative regulator of p53. COP1 is a RING finger-containing protein that targets p53 for degradation to the proteasome and is necessary for p53 turnover in normal and cancer cells. However, the association between COP1 and cancer remains to be determined. We performed expression analysis of COP1 in ovarian and breast cancer tissue microarrays. COP1 is significantly overexpressed in 81% (25 of 32) of breast and 44% (76 of 171) of ovarian adenocarcinoma as assessed by in situ hybridization and immunohistochemistry. Overexpression of COP1 correlated with a striking decrease in steady state p53 protein levels and attenuation of the downstream target gene, p21, in cancers that retain a wild-type p53 gene status. Overall, these results suggest that overexpression of COP1 contributes to the accelerated degradation of p53 protein in cancers and attenuates the tumor suppressor function of p53.
Researcher fails in legal bid to halt expression of concern by journal Diabetes
Authors: O. Dyer
Journal: BMJ (2015)

A Brazilian researcher who sued the American Diabetes Association to prevent its flagship journal Diabetes retracting four of his papers or publishing an expression of concern about his research has failed to convince a US federal judge to issue a restraining order.

Mario Saad, professor in the department of medicine at the State University of Campinas (Unicamp) in Sao Paulo, Brazil, alleged in his suit that the association had informed his university that Diabetes and other journals of the association would accept no submissions from Unicamp researchers until the situation was resolved.

The association’s panel on ethical scientific programs contacted Saad after readers raised concerns about potentially duplicated and manipulated images in two papers published in Diabetes in 2011 and 2007. Saad acknowledged the duplications but said that the image files had inadvertently been mixed up during editing. He offered a new image and proposed corrections.

The panel did not accept this explanation and asked the university to investigate the two papers. A …
Reduced Nitric Oxide in Sinus Epithelium of Patients with Radiologic Maxillary Sinusitis and Sepsis
Authors: Maria Deja, Thilo Busch, Sebastian Bachmann, Kerstin Riskowski, Valentina Câmpean, Brigitte Wiedmann, Michael Schwabe, Bertold Hell, Josef Pfeilschifter, Konrad J. Falke, Klaus Lewandowski
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Radiologic maxillary sinusitis is an important risk factor for development of bronchopneumonia in mechanically ventilated patients. Nitric oxide produced within the paranasal sinuses is considered to provide an antibacterial environment and to modulate mucociliary clearance function. We hypothesized that a reduced formation of nitric oxide might contribute to the compromised local host defense in radiologic maxillary sinusitis and measured nitric oxide levels directly within maxillary sinuses of septic patients with radiologic maxillary sinusitis (n = 11), whose sinuses were fenestrated to eliminate a possible septic focus. Data were compared with those of patients without airway inflammation (n = 11, control subjects). Despite local inflammation and infection, we found considerably lower maxillary nitric oxide levels than in control subjects (31 ± 10 versus 2,554 ± 385 parts per billion, mean ± standard error of the mean, p < 0.001). Consistently, immunohistochemical and in situ hybridization investigations revealed strongly reduced expression of inducible nitric oxide synthase. By applying ultrastructural immunolocalization, we identified cilia and microvilli of the maxillary sinus epithelium as the major nitric oxide production site in control subjects. Our findings provide evidence of markedly reduced nitric oxide production in maxillary sinuses of patients with radiologic maxillary sinusitis and sepsis, implicating impaired local host defense and an increased risk for secondary infections.
Pediatric-Onset and Adult-Onset Separation Anxiety Disorder Across Countries in the World Mental Health Survey
Authors: Derrick Silove, Jordi Alonso, Evelyn Bromet, Mike Gruber, Nancy Sampson, Kate Scott, Laura Andrade, Corina Benjet, Jose Miguel Caldas de Almeida, Giovanni De Girolamo, Peter de Jonge, Koen Demyttenaere, Fabian Fiestas, Silvia Florescu, Oye Gureje, Yanling He, Elie Karam, Jean-Pierre Lepine, Sam Murphy, Jose Villa-Posada, Zahari Zarkov, Ronald C. Kessler
Journal: American Journal of Psychiatry (2015)

Objective: The age-at-onset criterion for separation anxiety disorder was removed in DSM-5, making it timely to examine the epidemiology of separation anxiety disorder as a disorder with onsets spanning the life course, using cross-country data. Method: The sample included 38,993 adults in 18 countries in the World Health Organization (WHO) World Mental Health Surveys. The WHO Composite International Diagnostic Interview was used to assess a range of DSM-IV disorders that included an expanded definition of separation anxiety disorder allowing onsets in adulthood. Analyses focused on prevalence, age at onset, comorbidity, predictors of onset and persistence, and separation anxiety-related role impairment. Results: Lifetime separation anxiety disorder prevalence averaged 4.8% across countries (interquartile range [25th–75th percentiles]=1.4%−6.4%), with 43.1% of lifetime onsets occurring after age 18. Significant time-lagged associations were found between earlier separation anxiety disorder and subsequent onset of internalizing and externalizing DSM-IV disorders and conversely between these disorders and subsequent onset of separation anxiety disorder. Other consistently significant predictors of lifetime separation anxiety disorder included female gender, retrospectively reported childhood adversities, and lifetime traumatic events. These predictors were largely comparable for separation anxiety disorder onsets in childhood, adolescence, and adulthood and across country income groups. Twelve-month separation anxiety disorder prevalence was considerably lower than lifetime prevalence (1.0% of the total sample; interquartile range=0.2%–1.2%). Severe separation anxiety-related 12-month role impairment was significantly more common in the presence (42.4%) than absence (18.3%) of 12-month comorbidity. Conclusions: Separation anxiety disorder is a common and highly comorbid disorder that can have onset across the lifespan. Childhood adversity and lifetime trauma are important antecedents, and adverse effects on role function make it a significant target for treatment.