tbuckley/cabot-search huggingface dataset:
Direct conversion of mouse fibroblasts to hepatocyte-like cells using forced expression of endodermal transcription factors
Authors: Scott E. Swenson
Journal: Hepatology (2011)

The generation of functional hepatocytes independent of donor liver organs is of great therapeutic interest with regard to regenerative medicine and possible cures for liver disease. Induced hepatic differentiation has been achieved previously using embryonic stem cells or induced pluripotent stem cells. Particularly, hepatocytes generated from a patient's own induced pluripotent stem cells could theoretically avoid immunological rejection. However, the induction of hepatocytes from induced pluripotent stem cells is a complicated process that would probably be replaced with the arrival of improved technology. Overexpression of lineage-specific transcription factors directly converts terminally differentiated cells into some other lineages, including neurons, cardiomyocytes and blood progenitors; however, it remains unclear whether these lineage-converted cells could repair damaged tissues in vivo. Here we demonstrate the direct induction of functional hepatocyte-like (iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4, Hnf1a and Foxa3, and inactivation of p19Arf. iHep cells show typical epithelial morphology, express hepatic genes and acquire hepatocyte functions. Notably, transplanted iHep cells repopulate the livers of fumarylacetoacetate-hydrolase-deficient (Fah -/-) mice and rescue almost half of recipients from death by restoring liver functions. Our study provides a novel strategy to generate functional hepatocyte-like cells for the purpose of liver engineering and regenerative medicine.
A129: Unlike Fibroblast-like Synoviocytes from Oligoarticular Juvenile Idiopathic Arthritis, Fibroblast-like Synoviocytes From Polyarticular Subtype Do Not Display a Chondrocyte Phenotype
Authors: AnneMarie C. Brescia, Megan Simonds, Suzanne McCahan, Paul T. Fawcett, Carlos D. Rose
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

Condylar bony hypertrophy is functionally detrimental for children with JIA. Through gene expression profiling, we have identified dysregulated TGFb-signaling when fibroblast-like synoviocytes (FLS) from persistent oligoarticular JIA was compared to controls (heatmap). JIA FLS have a chondrocyte phenotype and may contribute to bony hypertrophy. In the current work, we have expanded the study to determine if FLS from extended oligoarticular (ext) and polyarticular (poly) subtypes also display a chondrocyte phenotype.



Methods:

Synovial fluid was obtained from our IRB-approved repository. Appropriate samples from steroid-naive knee joints were identified by chart review and JIA subtype classification. Control samples were obtained from remnant synovial fluid/tissue obtained from orthopedic procedures performed on non-arthritic joints. Both ext patients were on naprosyn and the first was also on methotrexate (mtx). Both poly patients were taking mtx and the first one was also taking naprosyn. Synovial fluid/tissue was plated in 6-well plates with 15% FBS DMEM media and passaged 3–6 times to obtain a pure sample of FLS. We examined secreted proteins in the cell culture supernatants from JIA and control FLS using western blot and ELISA.



Results:

FLS from ext (O) secrete increased amounts of BMP4, BMP2, aggrecan, collagen II and COMP when compared to both FLS from controls (C) and from poly (P) (western blot). By ELISA, the ext samples (Oligo) secreted more BMP4 protein than the controls (Ctrl) (p = 0.012) and the poly (Poly) (p < 0.001). COMP was significantly more highly secreted by the ext than the controls (p = 0.038) and the poly (p < 0.001). 



Conclusion:

Characterization of proteins expressed in cell culture media supernatants reveals that JIA FLS from oligoarticular subtype, either persistent or ext, but not from poly subtype, secrete chondrocyte differentiation markers. The difference more likely is related to differences in underlying disease pathogenesis between the subtypes rather than a medication effect since ¾ JIA patients were on mtx and no patients were on biologic agents at the time the synovial fluid was obtained. These characteristics may have implications for endochondral bone formation and local growth disturbances that are more prominent in oligoarticular than in poly JIA.
Physique traits of lightweight rowers and their relationship to competitive success
Authors: G J Slater, A J Rice, I Mujika, A G Hahn, K Sharpe, D G Jenkins
Journal: British Journal of Sports Medicine (2005)

Physique traits and their relationship to competitive success were assessed amongst lightweight rowers competing at the 2003 Australian Rowing Championships.Full anthropometric profiles were collected from 107 lightweight rowers (n = 65 males, n = 45 females) competing in the Under 23 and Open age categories. Performance assessments were obtained for 66 of these rowers based on results in the single sculls events. The relationship between physique traits and competitive success was then determined.Lower body fat (heat time estimate -8.4 s kg(-1), p<0.01), greater total body mass (heat time estimate -4.4 s kg(-1), p = 0.03), and muscle mass (heat time estimate -10.2 s kg(-1), p<0.01) were associated with faster 2000 m heat times.The more successful lightweight rowers were those who had lower body fat and greater total muscle mass.
Mevalonate kinase deficiency and IBD: shared genetic background
Authors: Anna Monica Bianco, Martina Girardelli, Diego Vozzi, Sergio Crovella, Giulio Kleiner, Annalisa Marcuzzi
Journal: Gut (2014)

Dear editor,

We read with interest the article entitled ‘Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease’ written by Uhlig1 and published by Gut . The study, describing the very early onset of intestinal inflammation in several orphan monogenic diseases, aimed at determining the presence of a link between the IBD-like phenotype shown by these rare diseases and the intestinal inflammation seen in typical IBD. The IBD aetiology is multifactorial: at present, genome-wide association studies have identified 163 susceptibility loci associated with an increased risk of developing IBD.2 Beside these identified genetic loci that provide little contribution to explain IBD hereditability, the number of monogenic diseases presenting IBD-like symptoms is however continuously increasing. These monogenic diseases usually exhibit very early onset and very severe symptoms; in addition, they are often unresponsive to common drugs (anti-inflammatory and immunosuppressive treatments, such as anti-TNFα).

In his article,1 Uhlig reports that …
BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells
Authors: Brian P. O'Connor, Vanitha S. Raman, Loren D. Erickson, W. James Cook, Lehn K. Weaver, Cory Ahonen, Ling-Li Lin, George T. Mantchev, Richard J. Bram, Randolph J. Noelle
Journal: The Journal of Experimental Medicine (2004)

Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by interleukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this α-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor–immunoglobulin treatment, inhibited PC survival in vitro and in vivo. Heightened expression of B cell maturation antigen (BCMA), and lowered expression of transmembrane activator and cyclophilin ligand interactor and BAFF receptor in PCs relative to resting B cells suggests a vital role of BCMA in PC survival. Affirmation of the importance of BCMA in PC survival was provided by studies in BCMA−/− mice in which the survival of long-lived bone marrow PCs was impaired compared with wild-type controls. These findings offer new insights into the molecular basis for the long-term survival of PCs.
Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression
Authors: Sucharita Bandyopadhyay, Rui Zhan, Asok Chaudhuri, Misako Watabe, Sudha K Pai, Shigeru Hirota, Sadahiro Hosobe, Taisei Tsukada, Kunio Miura, Yukio Takano, Ken Saito, Mary E Pauza, Sunao Hayashi, Ying Wang, Sonia Mohinta, Tomoyuki Mashimo, Megumi Iiizumi, Eiji Furuta, Kounosuke Watabe
Journal: Nature Medicine (2006)
Response and acclimatisation of symptomless smokers on changing to a low tar, low nicotine cigarette.
Authors: R G Rawbone
Journal: Thorax (1988)

Response and accnimatisation of symptomless smokers on changing to a low tar, low nicotine cigarette SIR,-The paper by Mr G Woodman and others (May 1987;42:336-41) concludes that for low delivery cigarettes ". . .smokers react to the lack of tar or nicotine, or both, by taking larger puffs while inhaling the same amount of smoke."This warrants further discussion.Smoke is defined by the authors as that which is labelled by the krypton-8 I m marker passing into the mainstream smoke through the burning cone.
Contribution of preterm delivery to perinatal mortality.
Authors: R W Rush, M J Keirse, P Howat, J D Baum, A B Anderson, A C Turnbull
Journal: BMJ (1976)

A detailed retrospective analysis was made of the records of 486 preterm infants, who accounted for 5-1% of all births during 1973 and 1974. Whereas preterm delivery did not contribute to perinatal mortality in terms of stillbirth, it outweighed all other causes in terms of early neonatal deaths. Preterm birth was responsible for 85% of the early neonatal deaths not due to lethal congenital deformities. Early neonatal mortality rates were closely linked both to gestational age and birth weight and to the reason for preterm birth. Early neonatal mortality was high (97 per 1000) when preterm labour was spontaneous, whether or not associated with material or fetal disease or with multiple pregnancy, but low (27 per 1000) when preterm delivery was elective. Preventing spontaneous preterm labour would considerably reduce neonatal mortality in our community.
Abnormal alpha 2-chain in type I collagen from a patient with a form of osteogenesis imperfecta.
Authors: P H Byers, J R Shapiro, D W Rowe, K E David, K A Holbrook
Journal: Journal of Clinical Investigation (1983)

Dermal fibroblasts in culture from a woman with a mild to moderate form of osteogenesis imperfecta synthesize two species of the pro alpha 2-chain of type I procollagen. One chain is normal. The abnormal chain has a slightly faster mobility than normal during electrophoresis in sodium dodecyl sulfate polyacrylamide gels. Analysis of cyanogen bromide peptides of the pro alpha-chain, the alpha-chain, and of the mammalian collagenase cleavage products of the pro alpha- and alpha-chains indicates that the abnormality is confined to the alpha 2(I)CB4 fragment and is consistent with loss of a short triple-helical segment. Type I collagen production was decreased, perhaps because the molecules that contained the abnormal chain were unstable, with a resultant alteration in the ratio of type III to type I collagen secreted into culture medium. Collagen fibrils in bone and skin had a normal periodicity but their diameters were 50% of control; the bone matrix was undermineralized. The structural abnormality in the alpha 2(I)-chain in this patient may affect molecular stability, intermolecular interactions, and collagen-mineral relationships that act to decrease the collagen content of tissues and affect the mineralization of bone.
The gastric secretory response to a continuous insulin infusion in the dog
Authors: R. R. Dozois, D. C. Carter, J. R. Kirkpatrick
Journal: Gut (1973)

The gastric acid response to graded doses of insulin given by continuous infusion was studied in four dogs, each surgically provided with a gastric fistula. All doses of insulin resulted in a prolonged plateau of hypoglycaemia and the degree of hypoglycaemia correlated significantly (p &lt;0·05) with the insulin dose, up to 0·15 u/kg hr. Similarly, graded doses of insulin (up to 0·15 u/kg hr) produced graded acid responses and both the peak acid output and the total acid output correlated significantly with blood glucose changes. No initial inhibitory phase of acid secretion followed the start of the infusion, but a dose-related delay in the onset of the acid response was observed. Our results indicate that insulin provides a quantitative glycopenic stimulus producing a quantitative vagal acid response.
Leucocyte cathepsin K affects atherosclerotic lesion composition and bone mineral density in low-density lipoprotein receptor deficient mice
Authors: J. Guo, I. Bot, R. de Nooijer, S. J. Hoffman, G. B. Stroup, E. A.L. Biessen, G. M. Benson, P. H.E. Groot, M. Van Eck, T. J.C. Van Berkel
Journal: Cardiovascular Research (2008)

Cathepsin K (CatK), an established drug target for osteoporosis, has been reported to be upregulated in atherosclerotic lesions. Due to its proteolytic activity, CatK may influence the atherosclerotic lesion composition and stability. In this study, we investigated the potential role of leucocyte CatK in atherosclerotic plaque remodelling.To assess the biological role of leucocyte CatK, we used the technique of bone marrow transplantation to selectively disrupt CatK in the haematopoietic system. Total bone marrow progenitor cells from CatK(+/+), CatK(+/-), and CatK(-/-) mice were transplanted into X-ray irradiated low-density lipoprotein receptor knockout (LDLr(-/-)) mice. The selective silencing of leucocyte CatK resulted in phenotypic changes in bone formation with an increased total bone mineral density in the CatK(-/-) chimeras and an effect of gene dosage. The absence of leucocyte CatK resulted in dramatically decreased collagen and increased macrophage content of the atherosclerotic lesions while lesion size was not affected. The atherosclerotic lesions also demonstrated less elastic lamina fragmentation and a significant increase in the apoptotic and necrotic area in plaques of mice transplanted with CatK(-/-) bone marrow.Leucocyte CatK is an important determinant of atherosclerotic plaque composition, vulnerability, and bone remodelling, rendering CatK an attractive target for pharmaceutical modulation in atherosclerosis and osteoporosis.
T-1095, a renal Na+-glucose transporter inhibitor, improves hyperglycemia in streptozotocin-induced diabetic rats
Authors: Tetsuya Adachi, Koichiro Yasuda, Yoshimasa Okamoto, Nobuyuki Shihara, Akira Oku, Kiichiro Ueta, Kazuyuki Kitamura, Akira Saito, Toshio Iwakura, Yuichiro Yamada, Hideki Yano, Yutaka Seino, Kinsuke Tsuda
Journal: Metabolism (2000)
Simultaneous detection of gastrointestinal pathogens with a multiplex Luminex-based molecular assay in stool samples from diarrhoeic patients
Authors: C. Mengelle, J.M. Mansuy, M.F. Prere, E. Grouteau, I. Claudet, N. Kamar, A. Huynh, G. Plat, M. Benard, N. Marty, A. Valentin, A. Berry, J. Izopet
Journal: Clinical Microbiology and Infection (2013)
Effect of insulinlike growth factor I on DNA and protein synthesis in cultured rat calvaria.
Authors: E Canalis
Journal: Journal of Clinical Investigation (1980)

Insulinlike growth Factor I (IGF I), a growth hormone-dependent peptide or somatomedin, was studied for its effects on bone formation by examining the synthesis of DNA, collagen, and noncollagen protein in cultures of 21-d fetal rat calvaria. IGF I caused a dose-dependent stimulation of the incorporation of [3H]thymidine into DNA at concentrations of 0.1--100 nM; the effect appeared after 6 h, was maximal at 12 h, and was sustained for 96 h. IGF I also increased the bone DNA content, IGF I at 0.1--3 nM had a small stimulatory effect on the incorporation of [3H]proline into collagenase-digestible protein (CDP) whereas 30 nM IGF I caused a two- to threefold increment and had a maximal effect. A smaller effect on the labeling of noncollagen protein (NCP) was also observed. The effect of CDP and NCP appeared and was maximal after 12 h and was sustained for 96 h. IGF I increased the total collagen content of bones. The IGF I stimulatory effect on the incorporation of [3H]thymidine was seen in both the periosteum and periosteum-free calvarium, whereas that on the labeling of CDP was seen only in the central, osteoblastic-rich, non-periosteal bone. Histological sections showed a 10-fold increase in the mitotic index after Colcemid arrest in IGF I-treated bones, the mitoses were equally distributed in the periosteum and central portions of the calvarium. Insulin had a stimulatory effect on the incorporation of [3H]proline into CDP and NCP and 1 nM--1 microM similar to the effect of IGF I. In contrast, high insulin concentrations (0.1 and 1 microM) were required to increase the incorporation of [3H]thymidine, and insulin did not affect DNA content. Cortisol decreased the stimulatory effect of IGF I on DNA labeling but greatly enhanced the stimulatory effect of IGF I on the incorporation of [3H]proline into CDP. Triiodothyronine and parathyroid hormone increased the incorporation of [3H]thymidine and were additive to IGF I. Triiodothyronine did not affect the labeling of CDP, but parathyroid hormone inhibited it and opposed the effect of IGF I. These studies indicate that IGF I stimulates bone DNA, collagen, and NCP synthesis in vitro. IGF I and insulin have similar effects on bone collagen synthesis but IGF I stimulates the synthesis of DNA at physiological concentrations, and insulin does not.
Genome-Wide Screening for Target Regions of Histone Deacetylases in Cardiomyocytes
Authors: Ruri Kaneda, Shuichi Ueno, Yoshihiro Yamashita, Young Lim Choi, Koji Koinuma, Shuji Takada, Tomoaki Wada, Kazuyuki Shimada, Hiroyuki Mano
Journal: Circulation Research (2005)

The acetylation status of core histones in cardiomyocytes has been linked to the development of cardiac hypertrophy and heart failure. Little is known, however, of the genes affected by abnormal histone acetylation in such pathological conditions. We recently developed a genome-wide screening method, differential chromatin scanning (DCS), to isolate genomic fragments associated with histones subject to differential acetylation. We have now applied DCS to H9C2 rat embryonic cardiomyocytes incubated with or without trichostatin A (TSA), a specific inhibitor of histone deacetylase (HDAC) activity. About 200 genomic fragments were readily isolated by DCS on the basis of the preferential acetylation of associated histones in TSA-treated cells. Quantitation of the amount of DNA in chromatin immunoprecipitates prepared with antibodies to acetylated histone H3 revealed that 37 of 38 randomly chosen DCS clones were preferentially precipitated from the TSA-treated cells, thus verifying the high fidelity of DCS. Epigenetic regulation of DCS clones was further confirmed in cells treated with sodium butyrate, another HDAC inhibitor, as well as in cardiac myocytes isolated from neonatal rats. The mRNA level of 9 (39%) of 23 genes corresponding to DCS clones changed in parallel with the level of histone acetylation in H9C2 cells. Furthermore, a physiological hypertrophic stimulus, cardiotrophin-1, affected the acetylation level of histones associated with genomic regions corresponding to certain DCS clones. Our data thus establish a genome-wide profile of HDAC targets in cardiomyocytes, which should provide a basis for further investigations into the role of epigenetic modification in cardiac disorders.
Extracellular matrix-modulated expression of human cell surface glycoproteins A42 and J143. Intrinsic and extrinsic signals determine antigenic phenotype.
Authors: W J Rettig, V V Murty, M J Mattes, R S Chaganti, L J Old
Journal: The Journal of Experimental Medicine (1986)

We have used serologic, biochemical, and genetic methods to characterize two stage-specific human differentiation antigens of neural and melanocytic cells: A42 (57,000 Mr glycoprotein) and J143 (140,000/30,000 Mr glycoprotein). The genes determining A42 and J143 cell surface expression in rodent-human hybrids were chromosomally mapped, and the respective human chromosomes were introduced into rodent cells derived from distinct differentiation lineages. Serologic analysis of the resulting hybrid clones has permitted the identification of two types of regulatory signals determining A42 and J143 expression. First, both antigens are expressed in hybrids constructed with antigen-positive human cells and also in certain hybrids constructed with antigen-negative human cells, indicating that intrinsic signals provided by the differentiation program of the rodent fusion partner induce antigen expression. Second, a series of human-mouse neuroblastoma hybrids, which are A42- or J143- when cultured on plastic surfaces, can be induced to express the antigens when cultured on substrates coated with extracellular matrix (ECM) produced by bovine corneal endothelial cells or fibronectin. This induction of antigen expression by extrinsic, ECM-derived signals is accompanied in the neuroblastoma hybrids by increased substrate adhesiveness and cell spreading and by characteristic changes in cell morphology. A similar program of phenotypic changes is also seen in spontaneous variants of human neuroblastoma and Ewing's sarcoma cells and in ECM-induced Ewing's sarcoma cells. These findings suggest that ECM-derived signals have a role analogous to mitogens and soluble differentiation factors in modulating differentiation phenotypes and tissue-specific patterns of cell surface antigen expression.
Role of p53 in Sensing Oxidative DNA Damage in Response to Reactive Oxygen Species-Generating Agents
Authors: Geetha Achanta, Peng Huang
Journal: Cancer Research (2004)

Abstract The tumor suppressor p53 plays an important role in the regulation of cellular response to DNA damage. Recent studies suggest that p53 is able to bind DNA with certain structural alterations in a sequence-independent manner and to interact with several molecules involved in DNA repair. This study was undertaken to test the hypothesis that p53 may participate in sensing oxidative DNA damage, the most frequently occurring spontaneous DNA lesion, and modulate its repair by the base excision repair (BER) machinery. Using synthetic DNA containing 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxoG), we showed that p53 was pulled down together with two BER proteins, human 8-oxoguanine glycosylase (hOGG1) and AP endonuclease (APE). Functional analysis showed that p53 significantly enhanced the sequential activities of hOGG1 and APE in excising the 8-oxoG nucleotide from DNA in vitro. The ability of p53 to enhance the removal of oxidized DNA bases was further demonstrated in vivo using a pair of p53 isogenic lines. HCT116 p53+/+ cells exhibit a more rapid removal of 8-oxoG from DNA than p53−/− cells exposed to the same levels of reactive oxygen species (ROS) stress. Together, these results suggest that p53 participates in sensing oxidative DNA damage and modulates BER function in response to persistent ROS stress.