tbuckley/cabot-search huggingface dataset:
Comparative ultrastructural study of rat livers preserved in euro-collins or university of wisconsin solution
Authors: Serge Fratté, Jean-Louis Gendrault, Anne-Marie Steffan, André Kirn
Journal: Hepatology (1991)

University of Wisconsin solution greatly lengthens the time liver storage is possible compared with all previous solutions used. To test whether this improvement is related to better preservation of the endothelial cell, which is thought to be the most vulnerable cell type in cold storage, we compared time-related ultrastructural changes in rat livers stored in this solution or in Euro-Collins solution. Rat livers were harvested after combined arterial and portal perfusion with the cold-storage solution. They were then preserved for different lengths of time in the same solution at 4 degrees C before being perfusion-fixed and processed for light and electron microscopy. The first preservation damage was noted in endothelial cells; the time course of the lesions was similar in both solutions. After 2 hr of storage, enlarged and ruptured fenestrae with many gaps were observed. Swollen at 4 hr, the endothelial cells became stringlike at 10 hr, leading to stripped sinusoidal walls. Hepatocytes appeared better preserved in University of Wisconsin solution. The amount of glycogen, maintained near the control level at 24 hr in the latter, decreased dramatically between 0 and 4 hr in Euro-Collins solution, as ultrastructurally observed and biochemically confirmed. Furthermore, sinusoidal obstruction by blebs originating from the hepatocytes and quantified by image analysis on electron micrographs was markedly delayed. It was significantly less pronounced in University of Wisconsin solution at 24 hr than in Euro-Collins solution at 2 hr (p less than or equal to 0.05). Our findings confirm that endothelial cells are highly susceptible to preservation damage and show that University of Wisconsin solution does not improve preservation during storage.(ABSTRACT TRUNCATED AT 250 WORDS)
The genome sequence of the model ascomycete fungus Podospora anserina
Authors: Eric Espagne, Olivier Lespinet, Fabienne Malagnac, Corinne Da Silva, Olivier Jaillon, Betina M Porcel, Arnaud Couloux, Jean-Marc Aury, Béatrice Ségurens, Julie Poulain, Véronique Anthouard, Sandrine Grossetete, Hamid Khalili, Evelyne Coppin, Michelle Déquard-Chablat, Marguerite Picard, Véronique Contamine, Sylvie Arnaise, Anne Bourdais, Véronique Berteaux-Lecellier, Daniel Gautheret, Ronald P de Vries, Evy Battaglia, Pedro M Coutinho, Etienne GJ Danchin, Bernard Henrissat, Riyad EL Khoury, Annie Sainsard-Chanet, Antoine Boivin, Bérangère Pinan-Lucarré, Carole H Sellem, Robert Debuchy, Patrick Wincker, Jean Weissenbach, Philippe Silar
Journal: Genome biology (2008)

Abstract Background The dung-inhabiting ascomycete fungus Podospora anserina is a model used to study various aspects of eukaryotic and fungal biology, such as ageing, prions and sexual development. Results We present a 10X draft sequence of P. anserina genome, linked to the sequences of a large expressed sequence tag collection. Similar to higher eukaryotes, the P. anserina transcription/splicing machinery generates numerous non-conventional transcripts. Comparison of the P. anserina genome and orthologous gene set with the one of its close relatives, Neurospora crassa , shows that synteny is poorly conserved, the main result of evolution being gene shuffling in the same chromosome. The P. anserina genome contains fewer repeated sequences and has evolved new genes by duplication since its separation from N. crassa , despite the presence of the repeat induced point mutation mechanism that mutates duplicated sequences. We also provide evidence that frequent gene loss took place in the lineages leading to P. anserina and N. crassa . P. anserina contains a large and highly specialized set of genes involved in utilization of natural carbon sources commonly found in its natural biotope. It includes genes potentially involved in lignin degradation and efficient cellulose breakdown. Conclusion The features of the P. anserina genome indicate a highly dynamic evolution since the divergence of P. anserina and N. crassa , leading to the ability of the former to use specific complex carbon sources that match its needs in its natural biotope.
Behavioral Phenotypes of Disc1 Missense Mutations in Mice
Authors: Steven J. Clapcote, Tatiana V. Lipina, J. Kirsty Millar, Shaun Mackie, Sheila Christie, Fumiaki Ogawa, Jason P. Lerch, Keith Trimble, Masashi Uchiyama, Yoshiyuki Sakuraba, Hideki Kaneda, Toshihiko Shiroishi, Miles D. Houslay, R. Mark Henkelman, John G. Sled, Yoichi Gondo, David J. Porteous, John C. Roder
Journal: Neuron (2007)
Distinct Methylation of the Interferon γ (IFN-γ) and Interleukin 3 (IL-3) Genes in Newly Activated Primary CD8+ T Lymphocytes: Regional IFN-γ Promoter Demethylation and mRNA Expression Are Heritable in CD44highCD8+ T Cells
Authors: David R. Fitzpatrick, Kym M. Shirley, Louise E. McDonald, Helle Bielefeldt-Ohmann, Graham F. Kay, Anne Kelso
Journal: The Journal of Experimental Medicine (1998)

Differential genomic DNA methylation has the potential to influence the development of T cell cytokine production profiles. Therefore, we have conducted a clonal analysis of interferon (IFN)-γ and interleukin (IL)-3 gene methylation and messenger (m)RNA expression in primary CD8+ T cells during the early stages of activation, growth, and cytokine expression. Despite similar distributions and densities of CpG methylation sites, the IFN-γ and IL-3 promoters exhibited differential demethylation in the same T cell clone, and heterogeneity between clones. Methylation patterns and mRNA levels were correlated for both genes, but demethylation of the IFN-γ promoter was widespread across &amp;gt;300 basepairs in clones expressing high levels of IFN-γ mRNA, whereas demethylation of the IL-3 promoter was confined to specific CpG sites in the same clones. Conversely, the majority of clones expressing low or undetectable levels of IFN-γ mRNA exhibited symmetrical methylation of four to six of the IFN-γ promoter CpG sites. Genomic DNA methylation also has the potential to influence the maintenance or stability of T cell cytokine production profiles. Therefore, we also tested the heritability of IFN-γ gene methylation and mRNA expression in families of clones derived from resting CD44lowCD8+ T cells or from previously activated CD44highCD8+ T cells. The patterns of IFN-γ gene demethylation and mRNA expression were faithfully inherited in all clones derived from CD44high cells, but variable in clones derived from CD44low cells. Overall, these findings suggest that differential genomic DNA methylation, including differences among cytokine genes, among individual T cells, and among T cells with different activation histories, is an important feature of cytokine gene expression in primary T cells.
Clinical applications of behavioral momentum
Authors: F. Charles Mace
Journal: Behavioral and Brain Sciences (2000)

An important measure of the validity and utility of basic behavioral research is the extent to which it can be applied in real life. Basic research on behavioral momentum and the model unifying choice and resistance to change (Nevin &amp; Grace 1999) has stimulated the development of behavioral technologies aimed at increasing the persistence of adaptive behavior and decreasing maladaptive choices.
Comment on “Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model”
Authors: Martin Tisdall, Axel Petzold
Journal: Science Translational Medicine (2012)

In a case study, the authors report an increase in phosphorylated neurofilament heavy chain, a marker of neuroaxonal damage, in the plasma of a blast-exposed patient immediately after injury. They suggest that this phosphoprotein may be a useful body fluid indicator of acute blast traumatic brain injury.
Lactic Acidosis in Lymphoma: Prompt Resolution of Acidosis With Therapy Directed at the Lymphoma
Authors: L. A. VANDERMOLEN, S. SWAIN, D. L. LONGO
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Lactic Acidosis in Lymphoma: Prompt Resolution of Acidosis With Therapy Directed at the Lymphoma Get access LOUIS A. VANDERMOLEN, LOUIS A. VANDERMOLEN 1Medicine Branch Clinical Oncology Program Division of Cancer Treatment National Cancer InstituteBethesda, MD 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar SANDRA SWAIN, SANDRA SWAIN 1Medicine Branch Clinical Oncology Program Division of Cancer Treatment National Cancer InstituteBethesda, MD 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar DAN L. LONGO DAN L. LONGO 2Biological Response Modifiers Program Division of Cancer Treatment National Cancer Institute-Frederick Cancer Research FacilityFrederick, MD 21701 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 13, 7 September 1988, Pages 1077–1078, https://doi.org/10.1093/jnci/80.13.1077 Published: 07 September 1988
Cisplatin Rapidly Down-regulates Its Own Influx Transporter hCTR1 in Cultured Human Ovarian Carcinoma Cells
Authors: Alison K. Holzer, Kuniyuki Katano, Leo W. J. Klomp, Stephen B. Howell
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Cisplatin (DDP)-resistant cells commonly exhibit reduced drug accumulation. Previous studies have shown that the major copper (Cu) influx transporter CTR1 controls the uptake of DDP in yeast and mammalian cells. The goal of this study was to examine the effect of Cu and DDP on the level and subcellular localization of hCTR1 protein in human ovarian carcinoma cells. Experimental Design: Cultured human ovarian carcinoma A2780 cells were exposed to DDP and Cu, and the effect on hCTR1 was determined using Western blot analysis and confocal digital deconvolution microscopy. Results: Loss of hCTR1 was triggered by DDP exposure in a concentration and time-dependent manner. Exposure to 0.5 μmol/L DDP for 5 minutes reduced hCTR1 levels and exposure to DDP concentrations ≥2 μmol/L caused almost complete disappearance. The loss of hCTR1 was observed within 1 minute of the start of exposure to 2 μmol/L DDP. Treatment of cells with 100 μmol/L Cu for 5 minutes produced a smaller effect. Pretreatment of cells with 2 μmol/L DDP for 5 minutes resulted in a 50% decrease in 64Cu uptake, demonstrating that the DDP-induced loss of hCTR1 detected by Western blot analysis and imaging was functionally significant. Conclusions: DDP down-regulated the amount of its major influx transporter in cultured human ovarian carcinoma cells in a concentration- and time-dependent manner. The effect was observed at DDP concentrations within the range found in the plasma of patients being treated with DDP, and it occurred very quickly relative to the half-life of the drug.
NKG<sub>2</sub>D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica
Authors: Christian Dejaco, Christina Duftner, Juman Al-Massad, Annette D Wagner, Joon-Keun Park, Johannes Fessler, Ariane Aigelsreiter, Franz Hafner, Sandra Vega, William Sterlacci, Beatrix Grubeck-Loebenstein, Alexander Tzankov, Thomas Ness, Luigi Boiardi, Carlo Salvarani, Michael Schirmer
Journal: Annals of the Rheumatic Diseases (2013)

Allergic asthma is currently considered a chronic airway inflammatory disorder associated with the presence of activated CD4<sup>+</sup> Th2-type lymphocytes, eosinophils, and mast cells. Interestingly, therapeutic strategies based on immune deviation and suppression have been shown to successfully attenuate the development of the asthma phenotype. In this investigation, we have for the first time used a genetically modified (GM) plant, narrow leaf lupin (<i>Lupinus angustifolius L.</i>), expressing a gene for a potential allergen (sunflower seed albumin) (SSA-lupin) to examine whether a GM plant/food-based vaccine strategy can be used to suppress the development of experimental asthma. We show that oral consumption of SSA-lupin promoted the induction of an Ag-specific IgG2a Ab response. Furthermore, we demonstrate that the plant-based vaccine attenuated the induction of delayed-type hypersensitivity responses and pathological features of experimental asthma (mucus hypersecretion, eosinophilic inflammation, and enhanced bronchial reactivity (airways hyperreactivity). The suppression of experimental asthma by SSA-lupin was associated with the production of CD4<sup>+</sup> T cell-derived IFN-γ and IL-10. Furthermore, we show that the specific inhibition of experimental asthma was mediated via CD4<sup>+</sup>CD45RB<sup>low</sup> regulatory T cells and IFN-γ. Thus, our data demonstrate that a GM plant-based vaccine can promote a protective immune response and attenuate experimental asthma, suggesting that plant-based vaccines may be potentially therapeutic for the protection against allergic diseases.
Decreased Lung Function in Female but not Male Subjects With Established Cystic Fibrosis–Related Diabetes
Authors: Erika J. Sims, Michael W. Green, Anil Mehta
Journal: Diabetes Care (2005)

OBJECTIVE—Although cystic fibrosis–related diabetes (CFRD) is associated with decreased lung function, sex is not known to influence CFRD. However, compared with male subjects with cystic fibrosis, female subjects with cystic fibrosis have increased morbidity. This study examines the association between female subjects with CFRD and poor lung function relative to male subjects using the percent predicted forced expiratory volume in 1 s (FEV1) as a surrogate measure of morbidity. RESEARCH DESIGN AND METHODS—We compared 323 patients with established CFRD with 489 cystic fibrosis control subjects with normal glucose tolerance (NGT) listed in the U.K. Cystic Fibrosis Database. Patients stratified by sex and chronic Pseudomonas aeruginosa infection were compared using binary logistic regression, and patients with new CFRD diagnoses were compared prospectively for the year 2002. RESULTS—CFRD in female subjects (but not male subjects) without chronic P. aeruginosa infection had a 20% lower percent predicted FEV1 compared with control subjects with NGT (95% CI −11.7 to −27.7; P &amp;lt; 0.0001). Genotype, age, treatment center, age at diagnosis of cystic fibrosis, pregnancy, liver function, or dose of pancreatic enzyme replacement therapy did not confound this female disadvantage. Comparison of female subjects with newly diagnosed CFRD free of chronic P. aeruginosa infection with matched control subjects with NGT showed no FEV1 disadvantage in the 1st year after CFRD diagnosis. CONCLUSIONS—Only female subjects with CFRD have significantly decreased lung function compared with sex-matched NGT control subjects. The absence of poor lung function in the first 12 months after diagnosis of diabetes suggests that an opportunity may exist to intervene and possibly prevent a decline in lung function, which can be as much as 20% in female subjects with CFRD.
Major Depression in Individuals With a History of Childhood Physical or Sexual Abuse: Relationship to Neurovegetative Features, Mania, and Gender
Authors: Robert D. Levitan, Sagar V. Parikh, Alain D. Lesage, Kathleen M. Hegadoren, Martha Adams, Sidney H. Kennedy, Paula N. Goering
Journal: American Journal of Psychiatry (1998)

Objective:Numerous studies have linked childhood trauma with depressive symptoms over the life span. However, it is not known whether particular neurovegetative symptom clusters or affective disorders are more closely linked with early abuse than are others. In a large community sample from Ontario, the authors examined whether a history of physical or sexual abuse in childhood was associated with particular neurovegetative symptom clusters of depression, with mania, or with both.Method:The World Health Organization Composite International Diagnostic Interview was used to assess 8,116 individuals aged 15–64 years. Each subject was asked about early physical and sexual abuse experiences on a structured supplement to the interview. Six hundred fifty-three cases of major depression were identified. Rates of physical and sexual abuse in depressive subgroups defined by typical and reversed neurovegetative symptom clusters (i.e., decreased appetite, weight loss, and insomnia versus increased appetite, weight gain, and hypersomnia, respectively) and by the presence or absence of lifetime mania were compared by gender.Results:A history of physical or sexual abuse in childhood was associated with major depression with reversed neurovegetative features, whether or not manic subjects were included in the analysis. A strong relationship between mania and childhood physical abuse was found. Across analyses there was a significant main effect of female gender on risk of early sexual abuse; however, none of the group-by-gender interactions predicted early abuse.Conclusions:These results suggest an association between early traumatic experiences and particular symptom clusters of depression, mania, or both in adults. Am J Psychiatry 1998; 155: 1746-1752
Significance of pre-S region–defective hepatitis B virus that emerged during exacerbation of chronic type B hepatitis
Authors: Masahito Minami, Takeshi Okanoue, Etsuro Nakajima, Koichiro Yasui, Keizo Kagawa, Kei Kashima
Journal: Hepatology (1993)

A defective form of the hepatitis B virus has been found in a patient with chronic type B hepatitis. Sequence analysis of the viral DNA after polymerase chain reaction amplification revealed a 117-base pair deletion (nucleotides 3129-53, subtype adr). This deletion includes the initiation codon of the pre-S2 region and a newly created in-frame stop codon in the pre-S1 region (nucleotide 3055) located 230 base pairs downstream from the pre-S1 initiation codon. This virus coexisted with the wild-type virus during the exacerbation period, as evidenced by an elevation of serum transaminase levels. It was not detected in the stable period, and the blood chemistry results were normal. We assayed antibodies against the mutationrelated region by enzyme immunoassay in serial serum samples to clarify the mechanism of the emergence of this variant virus. Antibodies against the pre-S2 region were negative; however, the antibody response against the pre-S1 epitopes coincided with the appearance of the variant virus. These findings suggest that an activated T-cell and B-cell response had developed against the pre-S1 region during hepatic inflammation in this patient and that, consequently, selection occurred for a pre-S antigen-defective mutant strain of the virus that might be resistant to such an immune response. (Hepatology 1993;17:558-563.)
Epigenetic Histone Methylation Modulates Fibrotic Gene Expression
Authors: Guangdong Sun, Marpadga A. Reddy, Hang Yuan, Linda Lanting, Mitsuo Kato, Rama Natarajan
Journal: Journal of the American Society of Nephrology (2010)

TGF-β1-induced expression of extracellular matrix (ECM) genes plays a major role in the development of chronic renal diseases such as diabetic nephropathy. Although many key transcription factors are known, mechanisms involving the nuclear chromatin that modulate ECM gene expression remain unclear. Here, we examined the role of epigenetic chromatin marks such as histone H3 lysine methylation (H3Kme) in TGF-β1-induced gene expression in rat mesangial cells under normal and high-glucose (HG) conditions. TGF-β1 increased the expression of the ECM-associated genes connective tissue growth factor, collagen-α1[Ι], and plasminogen activator inhibitor-1. Increased levels of chromatin marks associated with active genes (H3K4me1, H3K4me2, and H3K4me3), and decreased levels of repressive marks (H3K9me2 and H3K9me3) at these gene promoters accompanied these changes in expression. TGF-β1 also increased expression of the H3K4 methyltransferase SET7/9 and recruitment to these promoters. SET7/9 gene silencing with siRNAs significantly attenuated TGF-β1-induced ECM gene expression. Furthermore, a TGF-β1 antibody not only blocked HG-induced ECM gene expression but also reversed HG-induced changes in promoter H3Kme levels and SET7/9 occupancy. Taken together, these results show the functional role of epigenetic chromatin histone H3Kme in TGF-β1-mediated ECM gene expression in mesangial cells under normal and HG conditions. Pharmacologic and other therapies that reverse these modifications could have potential renoprotective effects for diabetic nephropathy.
Early signaling defects in human T cells anergized by T cell presentation of autoantigen.
Authors: J M LaSalle, P J Tolentino, G J Freeman, L M Nadler, D A Hafler
Journal: The Journal of Experimental Medicine (1992)

Major histocompatibility complex class II-positive human T cell clones are nontraditional antigen-presenting cells (APCs) that are able to simultaneously present and respond to peptide or degraded antigen, but are unable to process intact protein. Although T cell presentation of peptide antigen resulted in a primary proliferative response, T cells that had been previously stimulated by T cells presenting antigen were completely unresponsive to antigen but not to interleukin 2 (IL-2). In contrast, peptide antigen presented by B cells or DR2+ L cell transfectants resulted in T cell activation and responsiveness to restimulation. The anergy induced by T cell presentation of peptide could not be prevented by the addition of either autologous or allogeneic B cells or B7+ DR2+ L cell transfectants, suggesting that the induction of anergy could occur in the presence of costimulation. T cell anergy was induced within 24 h of T cell presentation of antigen and was long lasting. Anergized T cells expressed normal levels of T cell receptor/CD3 but were defective in their ability to release [Ca2+]i to both alpha CD3 and APCs. Moreover, anergized T cells did not proliferate to alpha CD2 monoclonal antibodies or alpha CD3 plus phorbol myristate acetate (PMA), nor did they synthesize IL-2, IL-4, or interferon gamma mRNA in response to either peptide or peptide plus PMA. In contrast, ionomycin plus PMA induced both normal proliferative responses and synthesis of cytokine mRNA, suggesting that the signaling defect in anergized cells occurs before protein kinase C activation and [Ca2+]i release.