tbuckley/cabot-search huggingface dataset:
Variability and Phylogenetic Incongruence of an SSU nrDNA Group I Intron in Artomyces, Auriscalpium, and Lentinellus (Auriscalpiaceae: Homobasidiomycetes)
Authors: E. B. Lickey
Journal: Molecular Biology and Evolution (2003)

Previous research has shown that a group I intron occurs in the SSU ribosomal DNA gene of isolates of Artomyces (Clavicorona, in part) and Lentinellus, but apparently it is absent in an Auriscalpium isolate. However, further investigation revealed that the intron is apparently absent in some species of Artomyces and Lentinellus and is present in at least one species of Auriscalpium. To examine this further, the presence or absence of the group I intron is reported for 13 species of Lentinellus, two species of Auriscalpium, and 16 species of Artomyces. The presence of the intron among the species was variable and is documented for seven species of Lentinellus, one species of Auriscalpium, and 12 species of Artomyces. Furthermore, the presence of the intron was variable among the isolates of several species, and variability of its presence was observed within single isolates, indicating inter-ribosomal repeat heterogeneity. Independent phylogenetic estimations were generated for the intron and nuclear ribosomal internal transcribed spacer regions (ITS). Tests of congruence for the two trees indicated that the data were heterogeneous. Some of the discontinuity between the two phylogenies is due to placement of the Ar. austropiperatus intron within the Lentinellus intron clade. Variability in the length of the intron was observed in populations of the pan-Northern Temperate species Ar. pyxidatus. This was due to the presence of an additional unknown insertional element found only within North American collections of Ar. pyxidatus and absent from European and Asian collections.
Phase I Pharmacokinetic and Pharmacodynamic Evaluation of Combined Valproic Acid/Doxorubicin Treatment in Dogs with Spontaneous Cancer
Authors: Luke A. Wittenburg, Daniel L. Gustafson, Douglas H. Thamm
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Histone deacetylase inhibitors (HDACi) are targeted anticancer agents with a well-documented ability to act synergistically with cytotoxic agents. We recently showed that the HDACi valproic acid sensitizes osteosarcoma cells to doxorubicin in vitro and in vivo. As there are no published reports on the clinical utility of HDACi in dogs with spontaneous cancers, we sought to determine a safe and biologically effective dose of valproic acid administered prior to a standard dose of doxorubicin. Methods: Twenty-one dogs were enrolled into eight cohorts in an accelerated dose-escalation trial consisting of pretreatment with oral valproic acid followed by doxorubicin on a three-week cycle. Blood and tumor tissue were collected for determination of serum valproic acid concentration and evaluation of pharmacodynamic effects by immunofluorescence cytochemistry and immunohistochemistry. Serum and complete blood counts were obtained for determination of changes in doxorubicin pharmacokinetics or hematologic effects. Results: All doses of valproic acid were well tolerated. Serum valproic acid concentrations increased linearly with dose. Doxorubicin pharmacokinetics were comparable with those in dogs receiving doxorubicin alone. A positive correlation was detected between valproic acid dose and histone hyperacetylation in peripheral blood mononuclear cells. No potentiation of doxorubicin-induced myelosuppression was observed. Histone hyperacetylation was documented in tumor and peripheral blood mononuclear cells. Responses included 2 of 21 complete, 3 of 21 partial, 5 of 21 stable disease, and 11 of 21 progressive disease. Conclusions: Valproic acid can be administered to dogs at doses up to 240 mg/kg/day prior to a standard dose of doxorubicin. In addition, we have developed the pharmacokinetic/pharmacodynamic tools necessary for future studies of novel HDACi in the clinical setting of canine cancer. Clin Cancer Res; 16(19); 4832–42. ©2010 AACR.
Systemic cytokine levels in community-acquired pneumonia and their association with disease severity
Authors: G. Antunes, S.A. Evans, J.L. Lordan, A.J. Frew
Journal: European Respiratory Journal (2002)

Pro-inflammatory and anti-inflammatory cytokines are important mediators in the host response to infection. In contrast to the pro-inflammatory cytokines little is known about anti-inflammatory cytokines in community-acquired pneumonia (CAP) and their relation to disease severity. Circulating levels of three pro-inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α) and two anti-inflammatory cytokines (IL-10, IL-1 receptor antagonist (IL-1ra)) were measured using an enzyme immunoassay on admission, day 3 and day 5 in 24 patients with CAP. The modified British Thoracic Society (BTS) prognostic rule and Acute Physiology and Chronic Health Evaluation (APACHE) II score were used to assess disease severity. IL-6, TNF-α, IL-10 and IL-1ra concentrations were detected in most patients on admission and decreased significantly on day 3 and day 5 in all survivors. A significant difference between the BTS high-risk and low-risk groups was only found for IL-6 (median (range) 477 pg·mL −1 (7.6–1402 pg·mL −1 ) versus 81.6 pg·mL −1 (0–943 pg·mL −1 ); p&lt;0.05). IL-6 also correlated with the APACHE II scores on admission. Concentrations of anti-inflammatory cytokines were elevated on admission in community-acquired pneumonia but they did not correlate with disease severity scores.
Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukemia
Authors: Alois Gratwohl, Ronald Brand, Jane Apperley, Anja V. Biezen, Giuseppe Bandini, Agnes Devergie, Anton Schattenberg, Francesco Frassoni, Cesare Guglielmi, Simona Iacobelli, Mauricette Michallet, Hans Jochen Kolb, Tapani Ruutu, Dietger Niederwieser
Journal: Blood (2002)
Incongruence in the diploid B-genome species complex of Glycine (Leguminosae) revisited: histone H3-D alleles versus chloroplast haplotypes
Authors: J. J. Doyle, J. L. Doyle, A. H. Brown
Journal: Molecular Biology and Evolution (1999)

Variation at the single-copy nuclear locus histone H3-D was surveyed in the diploid B-genome group of Glycine subgenus Glycine (Leguminosae: Papilionoideae), which comprises three named Australian species and a number of distinct but as yet not formally recognized taxa. A total of 23 alleles was identified in the 44 accessions surveyed. Only one individual was clearly heterozygous, which is not surprising given the largely autogamous breeding system of subgenus Glycine. Alleles differed by as many as 19 nucleotide substitutions, nearly all in the three introns; length variation was minimal. Phylogenetic analysis identified two shortest allele trees with very little homoplasy, suggesting that recombination has been rare. Both topological and data set incongruence were statistically significant between histone H3-D allele trees and trees inferred from chloroplast DNA haplotypes previously described from these same accessions. Whereas the distribution of H3-D alleles agrees well with morphologically based taxonomic groupings, chloroplast DNA haplotype polymorphisms transgress species boundaries, suggesting that the chloroplast genome is not tracking taxic relationships. Divergences among chloroplast DNA haplotypes involved in such transgressive patterns appear to be more recent than speciation events, suggesting hybridization rather than lineage sorting.
Epidermal Growth Factor Receptor Mutation Status and Adjuvant Chemotherapy With Uracil-Tegafur for Adenocarcinoma of the Lung
Authors: Hiroshi Suehisa, Shinichi Toyooka, Katsuyuki Hotta, Akiko Uchida, Junichi Soh, Yoshiro Fujiwara, Keitaro Matsuo, Mamoru Ouchida, Minoru Takata, Katsuyuki Kiura, Hiroshi Date
Journal: Journal of Clinical Oncology (2007)

Adjuvant chemotherapy with uracil-tegafur has been demonstrated to prolong survival among patients with resected lung adenocarcinomas. Epidermal growth factor receptor (EGFR) mutations have been reported to be present in lung adenocarcinomas. The present study evaluated whether the EGFR status could be used as a biologic predictor of the outcome of adjuvant chemotherapy with uracil-tegafur.The EGFR mutational status of 187 patients with resected lung adenocarcinomas was determined using a polymerase chain reaction-based assay for EGFR exons 19 and 21; the results were then correlated with the effect of adjuvant uracil-tegafur chemotherapy on survival. The antiproliferative effect of fluorouracil (FU) on adenocarcinoma cell lines with EGFR wild-type or mutant type status was examined by measuring the inhibitory concentrations at 50% (IC(50)s).Among the 187 patients, 68 received uracil-tegafur as adjuvant chemotherapy, and 119 were not treated with any chemotherapeutic agents. EGFR mutations were present in 79 patients (43%). Overall, the adjuvant chemotherapy with uracil-tegafur significantly prolonged survival compared with the control group (hazard ratio = 0.38; P = .005). The survival benefit of adjuvant chemotherapy with uracil-tegafur was also examined after stratifying the patients according to EGFR mutation status. Adjuvant chemotherapy significantly prolonged survival among patients with EGFR wild-type tumors (hazard ratio = 0.34; P = .013) but not among patients with EGFR mutant tumors. In an in vitro experiment, the IC(50)s of EGFR mutant cells to FU were higher than those of wild-type cells, indicating that EGFR wild-type cells are more sensitive to FU than mutant cells.EGFR status influenced the effect of adjuvant chemotherapy with uracil-tegafur. Adjuvant chemotherapy could be customized based on EGFR status.
Both Germ Line and Somatic Genetics of the p53 Pathway Affect Ovarian Cancer Incidence and Survival
Authors: Frank Bartel, Juliane Jung, Anja Böhnke, Elise Gradhand, Katharina Zeng, Christoph Thomssen, Steffen Hauptmann
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Although p53 is one of the most studied genes/proteins in ovarian carcinomas, the predictive value of p53 alterations is still ambiguous. Experimental Design: We performed analyses of the TP53 mutational status and its protein expression using immunohistochemistry. Moreover, the single nucleotide polymorphism SNP309 in the P2 promoter of the MDM2 gene was investigated. We correlated the results with age of onset and outcome from 107 patients with ovarian carcinoma. Results: In our study, we identified a large group of patients with p53 overexpression despite having a wild-type gene (49% of all patients with wild-type TP53). This was associated with a significantly shortened overall survival time (P = 0.019). Patients with p53 alterations (especially those with overexpression of wild-type TP53) were also more refractory to chemotherapy compared with patients with normal p53 (P = 0.027). The G-allele of SNP309 is associated with an earlier age of onset in patients with estrogen receptor–overexpressing FIGO stage III disease (P = 0.048). In contrast, in patients with FIGO stage III disease, a weakened p53 pathway (either the G-allele of SNP309 or a TP53 mutation) was correlated with increased overall survival compared with patients whose tumors were wild-type for both TP53 and SNP309 (P = 0.0035). Conclusion: Our study provides evidence that both germ line and somatic alterations of the p53 pathway influence the incidence and survival of ovarian carcinoma, and it underscores the importance of assessing the functionality of p53 in order to predict the sensitivity of platinum-based chemotherapies and patient outcome.
Lower circulating platelet counts and antiplatelet therapy independently predict better outcomes in patients with head and neck squamous cell carcinoma
Authors: Saleh Rachidi, Kristin Wallace, Terry A Day, Anthony J Alberg, Zihai Li
Journal: Journal of Hematology & Oncology (2014)

Head and neck squamous cell carcinoma (HNSCC) mortality rates have not shown significant reduction in decades. Platelets are being implicated in having cancer-promoting roles, an observation supported by the adverse outcomes associated with thrombocytosis in many malignancies associated with thrombocytosis. However, the prognostic significance of platelet counts in HNSCC is unknown. Here, we comprehensively investigate the predictive value of platelet counts at diagnosis and post-diagnosis antiplatelet treatment in the overall survival of HNSCC patients.The study population consists of 1051 pathologically confirmed HNSCC cases diagnosed between years 2000 and 2012 in a tertiary medical center. Platelet count was investigated as a predictor of survival by fitting Cox Proportional Hazards (CPH) regression models to generate Hazard Ratios (HR) and 95% confidence intervals (CI), while adjusting for age, sex, race, stage, treatment and smoking status. Finally, we evaluated the association between overall survival and antiplatelet medication intake after diagnosis.Multivariable analysis showed an increased death rate in patients with thromobocytosis [HR 2.37, 95% CI 1.60-3.50)] and high normal platelet counts [HR 2.20, 95% CI 1.58-3.05] compared to the reference middle normal group. Post-diagnosis treatment with antiplatelet medications was inversely associated with death rate [HR 0.76, 95% CI 0.58-0.99].Higher platelet counts were associated with poorer prognosis in HNSCC patients, whereas antiplatelet agents were associated with better prognosis. Antiplatelet agents warrant evaluation in preclinical and clinical settings as a way to improve survival in HNSCC.
The treatment of pyoderma gangrenosum with sodium cromoglycate
Authors: K. M. COCK, M. G. THORNE
Journal: British Journal of Dermatology (1980)

Journal Article The treatment of pyoderma gangrenosum with sodium cromoglycate Get access K. M. DE COCK, K. M. DE COCK Torbay Hospital, Lawes Bridge, Torquay, S. Devon Search for other works by this author on: Oxford Academic Google Scholar M. G. THORNE M. G. THORNE Torbay Hospital, Lawes Bridge, Torquay, S. Devon Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 102, Issue 2, 1 February 1980, Pages 231–233, https://doi.org/10.1111/j.1365-2133.1980.tb05698.x Published: 01 February 1980
Endocrine Disruptors in the Workplace, Hair Spray, Folate Supplementation, and Risk of Hypospadias: Case–Control Study
Authors: Gillian Ormond, Mark J. Nieuwenhuijsen, Paul Nelson, Mireille B. Toledano, Nina Iszatt, Sara Geneletti, Paul Elliott
Journal: Environmental Health Perspectives (2008)

Hypospadias is one of the most common urogenital congenital anomalies affecting baby boys. Prevalence estimates in Europe range from 4 to 24 per 10,000 births, depending on definition, with higher rates reported from the United States. Relatively little is known about potential risk factors, but a role for endocrine-disrupting chemicals (EDCs) has been proposed.Our goal was to elucidate the risk of hypospadias associated with occupational exposure of the mother to endocrine-disruptor chemicals, use of folate supplementation during pregnancy, and vegetarianism.We designed a case-control study of 471 hypospadias cases referred to surgeons and 490 randomly selected birth controls, born 1 January 1997-30 September 1998 in southeast England. Telephone interviews of mothers elicited information on folate supplementation during pregnancy and vegetarianism. We used a job exposure matrix to classify occupational exposure.In multiple logistic regression analysis, there were increased risks for self-reported occupational exposure to hair spray [exposed vs. nonexposed, odds ratio (OR) = 2.39; 95% confidence interval (CI), 1.40-4.17] and phthalate exposure obtained by a job exposure matrix (OR = 3.12; 95% CI, 1.04-11.46). There was a significantly reduced risk of hypospadias associated with of folate use during the first 3 months of pregnancy (OR = 0.64; 95% CI, 0.44-0.93). Vegetarianism was not associated with hypospadias risk.Excess risks of hypospadias associated with occupational exposures to phthalates and hair spray suggest that antiandrogenic EDCs may play a role in hypospadias. Folate supplementation in early pregnancy may be protective.
Prorenin Receptor Is Essential for Normal Podocyte Structure and Function
Authors: Yoichi Oshima, Kenichiro Kinouchi, Atsuhiro Ichihara, Mariyo Sakoda, Asako Kurauchi-Mito, Kanako Bokuda, Tatsuya Narita, Hideaki Kurosawa, Ge-Hong Sun-Wada, Yoh Wada, Taketo Yamada, Minoru Takemoto, Moin A. Saleem, Susan E. Quaggin, Hiroshi Itoh
Journal: Journal of the American Society of Nephrology (2011)

The prorenin receptor is an accessory subunit of the vacuolar H+-ATPase, suggesting that it has fundamental functions beyond activation of the local renin-angiotensin system. Podocytes express the prorenin receptor, but its function in these cells is unknown. Here, podocyte-specific, conditional, prorenin receptor-knockout mice died of kidney failure and severe proteinuria within 4 weeks of birth. The podocytes of these mice exhibited foot process effacement with reduced and altered localization of the slit-diaphragm proteins nephrin and podocin. Furthermore, the podocytes contained numerous autophagic vacuoles, confirmed by enhanced accumulation of microtubule-associated protein 1 light chain 3-positive intracellular vesicles. Ablation of the prorenin receptor selectively suppressed expression of the V0 c-subunit of the vacuolar H+-ATPase in podocytes, resulting in deacidification of intracellular vesicles. In conclusion, the prorenin receptor is important for the maintenance of normal podocyte structure and function.
Lupeol, a Novel Androgen Receptor Inhibitor: Implications in Prostate Cancer Therapy
Authors: Hifzur Rahman Siddique, Shrawan Kumar Mishra, R. Jeffery Karnes, Mohammad Saleem
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Conventional therapies to treat prostate cancer (CaP) of androgen-dependent phenotype (ADPC) and castration-resistant phenotype (CRPC) are deficient in outcome which has necessitated a need to identify those agents that could target AR for both disease types. We provide mechanism-based evidence that lupeol (Lup-20(29)-en-3b-ol) is a potent inhibitor of androgen receptor (AR) in vitro and in vivo. Experimental Design: Normal prostate epithelial cell (RWPE-1), LAPC4 (wild functional AR/ADPC), LNCaP (mutant functional/AR/ADPC), and C4-2b (mutant functional/AR/CRPC) cells were used to test the anti-AR activity of lupeol. Cells grown under androgen-rich environment and treated with lupeol were tested for proliferation, AR transcriptional activity, AR competitive ligand binding, AR–DNA binding, and AR–ARE/target gene binding. Furthermore, in silico molecular modeling for lupeol–AR binding was done. Athymic mice bearing C4-2b and LNCaP cell–originated tumors were treated intraperitoneally with lupeol (40 mg/kg; 3 times/wk) and tumor growth and surrogate biomarkers were evaluated. To assess bioavailability, lupeol serum levels were measured. Results: Lupeol significantly inhibited R1881 (androgen analogue) induced (i) transcriptional activity of AR and (ii) expression of PSA. Lupeol (i) competed antagonistically with androgen for AR, (ii) blocked the binding of AR to AR-responsive genes including PSA, TIPARP, SGK, and IL-6, and (iii) inhibited the recruitment of RNA Pol II to target genes. Lupeol sensitized CRPC cells to antihormone therapy. High-performance liquid chromatography analysis showed that lupeol is bioavailable to mice. Lupeol inhibited the tumorigenicity of both ADPC and CRPC cells in animals. Serum and tumor tissues exhibited reduced PSA levels. Conclusion: Lupeol, an effective AR inhibitor, could be developed as a potential agent to treat human CaP. Clin Cancer Res; 17(16); 5379–91. ©2011 AACR.
Endoplasmic reticulum heat shock protein gp96 maintains liver homeostasis and promotes hepatocellular carcinogenesis
Authors: Saleh Rachidi, Shaoli Sun, Bill X. Wu, Elizabeth Jones, Richard R. Drake, Besim Ogretmen, L. Ashley Cowart, Christopher J. Clarke, Yusuf A. Hannun, Gabriela Chiosis, Bei Liu, Zihai Li
Journal: Journal of Hepatology (2014)
Intra-Individual Variation in DNA Methylation of IFNγ and IL4 Over Days
Authors: J.S. Kuriakose, D. Torrone, K. Gauvey-Kern, S. Hsu, M. Niedzwiecki, H. Jiang, F. Perera, R.L. Miller
Journal: Journal of Allergy and Clinical Immunology (2011)
Role of bronchoscopy in treatment of plastic bronchitis
Authors: Valentina Molodtsova, Svetlana Sobchenko
Journal: European Respiratory Journal (2013)

Aim: diagnosis and therapy of plastic bronchitis using bronchofibroscopy (BFS) with endobronchial administration of mucolytics.  Methods. Efficiency of different bronchoscopic methods was analyzed in therapy of 20 pts (6 men, 14 women) with plastic bronchitis who were observed from 1990 to 2012. The average age was 40,2 yr (21-63 years). X-ray study revealed signs of bilateral lower lobar pneumonia (1 pt), segmental atelectasis in right lung (11 pts) and left one (9 pts).  Results. In all pts diagnostic BFS revealed hyperemia, thickening of mucosa, narrowing and swelling of mouths of lobar and segmental bronchi in sites of occlusion with dense, rubbery-like, mucous content that is not amenable to vacuum aspiration. Occlusion of mouths of segmental bronchi B8-10 was observed in 11 pts. Casts were removed from segmental bronchi (6 pts) and middle-lobar bronchus (2 pts). Therapeutic BFSs (2-5) with segmental bronchoalveolar lavage with saline in combination with bronchodilators and mucolytics were performed in all pts. With no effect casts of bronchial tubes were removed with forceps, brush, balloon Fogarty. One pt was subjected to rigid BFS to retrieve the large cast from middle-lobar bronchus. As a result of endobronchial therapy the full recovery of bronchial lumens was achieved in all pts. The complete unfolding of atelectasis was confirmed by X-ray and CT scan of the chest.  Conclusion. Plastic bronchitis with bronchial casts that occlude lumens of segmental bronchi is a rare disease. Often they appear in ineffective treatment of long course of asthma and COPD exacerbations. Therapeutic BFS with using mucolytic drugs is the gold standard treatment for pts with plastic bronchitis.
Genetic and Molecular Bases of Neurogenesis in Drosophila Melanogaster
Authors: J A Campos-Ortega, Y N Jan
Journal: Annual Review of Neuroscience (1991)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More