tbuckley/cabot-search huggingface dataset:
ATP binding cassette transporter gene expression in rat liver progenitor cells
Authors: J.E. Ros, T.A.D. Roskams, M. Geuken, R. Havinga, P.L. Splinter, B.E. Petersen, N.F. LaRusso, D.M. van der Kolk, F. Kuipers, K.N. Faber, M.R. Müller, P.L.M. Jansen
Journal: Gut (2003)

<b>Background and aim:</b> Liver regeneration after severe liver damage depends in part on proliferation and differentiation of hepatic progenitor cells (HPCs). Under these conditions they must be able to withstand the toxic milieu of the damaged liver. ATP binding cassette (ABC) transporters are cytoprotective efflux pumps that may contribute to the preservation of these cells. The aim of this study was to determine the ABC transporter phenotype of HPCs. <b>Methods:</b> HPC activation was studied in rats treated with 2- acetylaminofluorene (2-AAF) followed by partial hepatectomy (PHx). ABC transporter gene expression was determined by real time detection reverse transcription-polymerase chain reaction in isolated HPCs, hepatocytes, cholangiocytes, and cultured progenitor cell-like RLF ϕ 13 cells and by immunohistochemistry of total liver samples. ABC transporter efflux activity was studied in RLF ϕ 13 cells by flow cytometry. <b>Results:</b> 2-AAF/PHx treated animals showed increased hepatic mRNA levels of the genes encoding multidrug resistance proteins <i>Mdr1b</i>, <i>Mrp1</i>, and <i>Mrp3</i>. Immunohistochemistry demonstrated expression of Mrp1 and Mrp3 proteins in periportal progenitor cells and of the Mdr1b protein in periportal hepatocytes. Freshly isolated Thy-1 positive cells and cultured RLF ϕ 13 progenitor cells highly expressed <i>Mrp1</i> and <i>Mrp3</i> mRNA while the hepatocyte specific transporters <i>Mdr2</i>, <i>Bsep</i>, <i>Mrp2</i>, and <i>Mrp6</i> were only minimally expressed. Blocking Mrp activity by MK-571 resulted in accumulation of the Mrp specific substrate carboxyfluorescein in RLF ϕ 13 cells. <b>Conclusion:</b> HPCs express high levels of active Mrp1 and Mrp3. These may have a cytoprotective role in conditions of severe hepatotoxicity.
High glucose increases prostaglandin E2 synthesis in human peritoneal mesothelial cells
Authors: T Sitter, B Haslinger, S Mandl, H Fricke, E Held, A Sellmayer
Journal: Journal of the American Society of Nephrology (1998)

Peritoneal mesothelial cells are considered the predominant source of peritoneal prostanoid formation because they represent the largest resident cell population in the peritoneal cavity. The present study was designed to evaluate the effect of D-glucose, which is widely used in commercially available peritoneal dialysis fluids as an osmotic compound, on the synthesis of prostaglandins in cultured human mesothelial cells (HMC). Analysis of eicosanoid synthesis in HMC by reversed-phase HPLC revealed that 6-keto-PGF1alpha, the spontaneous hydrolysis product of prostacyclin (PGI2), and prostaglandin E2 (PGE2) were the main eicosanoids produced. Addition of D-glucose resulted in a time- and concentration-dependent (30 to 120 mM) increase in PGE2 production in HMC (24 h, 90 mM: 3.9+/-0.5 ng/10(5) cells versus 2.3+/-0.3 in untreated cells; P < 0.05). Mannitol (90 mM) or L-glucose (90 mM). nonmetabolizable osmotic compounds, also led to a significant (P < 0.05) but less intense increase in PGE2 synthesis (3.3+/-0.4 and 3.2+/-0.5 ng/10(5) cells, respectively). Increased PGE2 synthesis was completely blunted by coincubation with the specific protein kinase C (PKC) inhibitor Ro 31-8220 or downregulation of PKC activity by preincubation with phorbol myristate acetate for 16 h. Furthermore, coincubation with PD 98059, an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway, also inhibited increased PGE2 synthesis by D-glucose or mannitol. In contrast, the iso-osmolar glucose polymer icodextrin, which is used as an alternative to D-glucose in peritoneal dialysis solutions, had no effect on PGE2 synthesis. These data indicate that D-glucose and metabolically inert sugars increase PGE2 synthesis in HMC at least in part by hyperosmolarity and that this effect requires activation of PKC and the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway of intracellular signaling.
Targeting Superficial or Nodular Basal Cell Carcinoma with Topically Formulated Small Molecule Inhibitor of Smoothened
Authors: Tracy Tang, Jean Y. Tang, Dongwei Li, Mike Reich, Christopher A. Callahan, Ling Fu, Robert L. Yauch, Frank Wang, Karen Kotkow, Kris S. Chang, Elana Shpall, Angela Wu, Lee L. Rubin, James C. Marsters, Ervin H. Epstein, Ivor Caro, Frederic J. de Sauvage
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Inappropriate activation of the Hedgehog (Hh) signaling pathway in skin is critical for the development of basal cell carcinomas (BCC). We have investigated the anti-BCC efficacy of topically-applied CUR61414, an inhibitor of the Hh signal transduction molecule Smoothened. Experimental Design: In preclinical studies, we used a depilatory model to evaluate the ability of topical formulations of CUR61414 to repress Hh responsive cells found at the base of hair follicles in normal skin. We also tested the in vivo effects of topical CUR61414 on murine BCCs developed in Ptch1 +/− K14-CreER2 p53 fl/fl mice. In a phase I clinical study, we evaluated the safety, tolerability, and efficacy of a multidose regimen of CUR61414 (0.09%, 0.35%, 1.1%, and 3.1%) applied topically to human superficial or nodular BCCs for up to 28 days. Results: In mice, topical CUR61414 significantly inhibited skin Hh signaling, blocked the induction of hair follicle anagen, and shrank existing BCCs. However, we observed no clinical activity of this formulation in human superficial or nodular BCCs in a phase I clinical study. Conclusions: Our data highlight some of the challenges of translating preclinical experience into successful human results for a topical anticancer agent. Clin Cancer Res; 17(10); 3378–87. ©2011 AACR.
Structure, Expression, and Function of Atrial Natriuretic Factor in Extraatrial Tissues*
Authors: JOLANTA GUTKOWSKA, MONA NEMER
Journal: Endocrine Reviews (1989)

I. Introduction THE MAINTENANCE of water and salt balance in the continuously changing conditions of external and internal environment is one of the most important body functions. This function is maintained by the complex interplay of several neuronal and hormonal systems such as renin-angiotensin-aldosterone, vasopressin, and a recently discovered cardiac hormone. Indeed, cardiac myocytes synthesize and secrete into the blood stream (1) a biologically potent peptide, atrial natriuretic factor (ANF), whose existence was first discovered by de Bold and co-workers in 1981 (2). ANF in a 28 amino acid (AA) peptide (ANF-99-126)1 which is present at the carboxyl end of a larger precursor molecule [(ANF 1-126; (3)]. The peptide has been found and characterized in the heart of several mammalians (including human, rat, rabbit, bovine, etc.) birds and amphibians (4) and complementary DNA (cDNA) and genomic clones encoding the ANF precursor have been obtained from several species (5). The ANF sequence is highly con...
Lung function predicts lung cancer
Authors: R. Young, R. Hopkins
Journal: European Respiratory Journal (2010)

Lung function predicts lung cancerTo the Editors:We read with great interest the recent article by CALABRO et al. [1] showing the close relationship between obstructive lung disease and lung cancer.In particular, we are interested in their suggestion that spirometry might play a very useful role in improving patient selection for targeted lung cancer screening.
THE BLOOD VESSELS OF THE SCALP IN PATIENTS WTTH ALOPECIA AREATA BEFORE AND AFTER CORTICOSTEHOID THERAPY
Authors: P. POPCHRISTOV, A. KONSTANTINOV, E. OBRESHKOVA
Journal: British Journal of Dermatology (1968)

SUMMARY.— The blood supply to the hair follicles has been studied by alkaline phosphatase staining in 31 patients with alopecia areata or totalis. Biopsies were taken before, during and after treatment with intralesional or systemic corticosteroids. The restoration of the normal pattern of the skin vasculature accompanies the re‐establishment of normal hair growth, whether this is induced by corticosteroids or occurs spontaneously.
VITAMIN B12 DEFICIENCY AS A WORLDWIDE PROBLEM
Authors: Sally P. Stabler, Robert H. Allen
Journal: Annual Review of Nutrition (2004)

Pernicious anemia is a common cause of megaloblastic anemia throughout the world and especially in persons of European or African descent. Dietary deficiency of vitamin B12 due to vegetarianism is increasing and causes hyperhomocysteinemia. The breast-fed infant of a vitamin B12-deficient mother is at risk for severe developmental abnormalities, growth failure, and anemia. Elevated methylmalonic acid and/or total homocysteine are sensitive indicators of vitamin B12-deficient diets and correlate with clinical abnormalities. Dietary vitamin B12 deficiency is a severe problem in the Indian subcontinent, Mexico, Central and South America, and selected areas in Africa. Dietary vitamin B12 deficiency is not prevalent in Asia, except in vegetarians. Areas for research include intermittent vitamin B12 supplement dosing and better measurements of the bioavailability of B12 in fermented vegetarian foods and algae.
Effects of acetazolamide in patients with the sleep apnoea syndrome.
Authors: H Tojima, F Kunitomo, H Kimura, K Tatsumi, T Kuriyama, Y Honda
Journal: Thorax (1988)

There is as yet no convincing evidence that acetazolamide, a carbonic anhydrase inhibitor, is effective in obstructive sleep apnoea. A study was therefore designed to examine the effect of acetazolamide (250 mg/day) on sleep events and ventilatory control during wakefulness in nine patients with the sleep apnoea syndrome. In eight of the nine patients the apnoea index and the total duration of apnoea were reduced by acetazolamide, and the mean (SEM) apnoea index of all patients changed from 25.0 (6.7) to 18.1 (5.8) episodes an hour. Furthermore, the total time of arterial oxygen desaturation (SaO2)--more than 4% depression in SaO2 from the baseline sleeping level--divided by total sleep time was also significantly decreased and its mean (SEM) value improved from 24.1 (7.9) to 13.6 (4.8)% of total sleep time. Five of the seven patients with varying degrees of daytime hypersomnolence had their symptoms obviously improved. There was no patient whose predominant type of apnoea was converted from the obstructive to the central type, or vice versa. In the studies of wakefulness, metabolic acidosis, an increase of arterial oxygen tension (PaO2) and a decrease of arterial carbon dioxide tension (PaCO2) were observed. The slopes of the occlusion pressure response and the ventilatory response to carbon dioxide increased, and the carbon dioxide ventilatory response line shifted to the left. It is suggested that acetazolamide cannot remove apnoea completely but has a beneficial effect in mild cases of obstructive sleep apnoea through an augmentation of central (CO2, H+) drive and a stabilising effect on ventilatory control.
Native and recombinant human hepatocyte growth factors are highly potent promoters of DNA synthesis in both human and rat hepatocytes.
Authors: A J Strain, T Ismail, H Tsubouchi, N Arakaki, T Hishida, N Kitamura, Y Daikuhara, P McMaster
Journal: Journal of Clinical Investigation (1991)

Human hepatocyte growth factor (hHGF) has recently been expressed as a recombinant polypeptide from Chinese hampster ovary cell transfectants. Using a primary rat hepatocyte bioassay, we have tested the biological activity of recombinant hHGF and compared it with native hHGF. Dose-response curves were almost identical, with half-maximal stimulation of DNA synthesis at 1-2 ng/ml (equivalent to approximately 10 pM). S-phase labeling index was similarly enhanced and numerous mitotic cells were observed. Recombinant and native hHGF also stimulated DNA synthesis and S-phase labeling index in primary adult human hepatocytes. Human cells were more responsive than rat hepatocytes, with recombinant hHGF slightly more potent than native hHGF (half-maximal stimulation 0.3 and 0.6 ng/ml, respectively). Since HGF levels rise in patients with fulminant hepatic failure and in animals after partial hepatectomy or administration of hepatotoxins, situations where liver regeneration occurs, HGF is suggested to play a key role in regulation of hepatic growth. The high potency of the factor on human hepatocytes reinforces its candidacy as a critical mitogen in human liver growth. The availability of a recombinant hHGF opens the way for in vivo experimental studies and to the possibility of using hHGF as a clinical therapeutic agent, either alone or in combination with other factors.
WT1 peptide-specific T cells generated from peripheral blood of healthy donors: possible implications for adoptive immunotherapy after allogeneic stem cell transplantation
Authors: G Weber, J Karbach, S Kuçi, H Kreyenberg, A Willasch, E Koscielniak, T Tonn, T Klingebiel, W S Wels, E Jäger, P Bader
Journal: Leukemia (2009)
MUC1 gene overexpressed in breast cancer: structure and transcriptional activity of the MUC1 promoter and role of estrogen receptor alpha (ERalpha) in regulation of the MUC1 gene expression.
Authors: Joseph Z Zaretsky, Itay Barnea, Yael Aylon, Marat Gorivodsky, Daniel H Wreschner, Iafa Keydar
Journal: Molecular Cancer (2006)

The MUC1 gene encodes a mucin glycoprotein(s) which is basally expressed in most epithelial cells. In breast adenocarcinoma and a variety of epithelial tumors its transcription is dramatically upregulated. Of particular relevance to breast cancer, steroid hormones also stimulate the expression of the MUC1 gene. The MUC1 gene directs expression of several protein isoforms, which participate in many crucial cell processes. Although the MUC1 gene plays a critical role in cell physiology and pathology, little is known about its promoter organization and transcriptional regulation. The goal of this study was to provide insight into the structure and transcriptional activity of the MUC1 promoter. Using TRANSFAC and TSSG soft-ware programs the transcription factor binding sites of the MUC1 promoter were analyzed and a map of transcription cis-elements was constructed. The effect of different MUC1 promoter regions on MUC1 gene expression was monitored. Different regions of the MUC1 promoter were analyzed for their ability to control expression of specific MUC1 isoforms. Differences in the expression of human MUC1 gene transfected into mouse cells (heterologous artificial system) compared to human cells (homologous natural system) were observed. The role of estrogen on MUC1 isoform expression in human breast cancer cells, MCF-7 and T47D, was also analyzed. It was shown for the first time that synthesis of MUC1/SEC is dependent on estrogen whereas expression of MUC1/TM did not demonstrate such dependence. Moreover, the estrogen receptor alpha, ERα, could bind in vitro estrogen responsive cis-elements, EREs, that are present in the MUC1 promoter. The potential roles of different regions of the MUC1 promoter and ER in regulation of MUC1 gene expression are discussed. Analysis of the structure and transcriptional activity of the MUC1 promoter performed in this study helps to better understand the mechanisms controlling transcription of the MUC1 gene. The role of different regions of the MUC1 promoter in expression of the MUC1 isoforms and possible function of ERα in this process has been established. The data obtained in this study may help in development of molecular modalities for controlled regulation of the MUC1 gene thus contributing to progress in breast cancer gene therapy.
Differentially Regulated Micro-RNAs and Actively Translated Messenger RNA Transcripts by Tumor Suppressor p53 in Colon Cancer
Authors: Yaguang Xi, Reut Shalgi, Oystein Fodstad, Yitzhak Pilpel, Jingfang Ju
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The aim of this study was to investigate the role of p53 in regulating micro-RNA (miRNA) expression due to its function as a transcription factor. In addition, p53 may also affect other cellular mRNA gene expression at the translational level either via its mediated miRNAs or due to its RNA-binding function. Experimental Design: The possible interaction between p53 and miRNAs in regulating gene expression was investigated using human colon cancer HCT-116 (wt-p53) and HCT-116 (null-p53) cell lines. The effect of p53 on the expression of miRNAs was investigated using miRNA expression array and real-time quantitative reverse transcription-PCR analysis. Results: Our investigation indicated that the expression levels of a number of miRNAs were affected by wt-p53. Down-regulation of wt-p53 via small interfering RNA abolished the effect of wt-p53 in regulating miRNAs in HCT-116 (wt-p53) cells. Global sequence analysis revealed that over 46% of the 326 miRNA putative promoters contain potential p53-binding sites, suggesting that some of these miRNAs were potentially regulated directly by wt-p53. In addition, the expression levels of steady-state total mRNAs and actively translated mRNA transcripts were quantified by high-density microarray gene expression analysis. The results indicated that nearly 200 cellular mRNA transcripts were regulated at the posttranscriptional level, and sequence analysis revealed that some of these mRNAs may be potential targets of miRNAs, including translation initiation factor eIF-5A, eIF-4A, and protein phosphatase 1. Conclusion: To the best of our knowledge, this is the first report demonstrating that wt-p53 and miRNAs interact in influencing gene expression and providing insights of how p53 regulates genes at multiple levels via unique mechanisms.
Reducing deprivation to level of least deprived could cut infant deaths by a quarter
Authors: A. O'Dowd
Journal: BMJ (2009)

Almost a quarter of all infant deaths in England and Wales could be prevented if deprivation were cut to the level of the least deprived, says a report from the Office for National Statistics and the London School of Hygiene and Tropical Medicine . 

The researchers base their figures on the numbers of live singleton births in England and Wales in 2005-6 and indicators of deprivation.

Of 1.3 million live births in England and Wales in this period, 6491 were registered as infant deaths. The infant mortality rate for singleton births was 4.4 per 1000 live births compared with 23.5 per 1000 for multiple births.

Low birth …
ULTRA-VIOLET LIGHT
Authors: P. R. Peacock
Journal: BMJ (1925)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following ULTRA-VIOLET LIGHT Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Lifetime prevalence, characteristics, and associated problems of non-consensual sex in men: cross sectional survey
Authors: A. Coxell, M. King, G. Mezey, D. Gordon
Journal: BMJ (1999)

Two patients are described in whom computerised tomography revealed contrast-enhanced lesions in the early stages of multiple sclerosis. Such lesions may be differentiated from tumours by their transient nature, lack of space-occupying effect, and localisation in the white matter. Contrast enhancement in demyelinating disease is probably related to local breakdown of the blood-brain barrier.
Probing the Molecular Structure of the Voltage-Dependent Sodium Channel
Authors: R L Barchi
Journal: Annual Review of Neuroscience (1988)

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
Risk factors for rehospitalisation in COPD: role of health status, anxiety and depression
Authors: G. Gudmundsson, T. Gislason, C. Janson, E. Lindberg, R. Hallin, C. S. Ulrik, E. Brøndum, M. M. Nieminen, T. Aine, P. Bakke
Journal: European Respiratory Journal (2005)

The aim of the present study was to analyse the risk of rehospitalisation in patients with chronic obstructive pulmonary disease and associated risk factors. This prospective study included 416 patients from a university hospital in each of the five Nordic countries. Data included demographic information, spirometry, comorbidity and 12 month follow-up for 406 patients. The hospital anxiety and depression scale and St. George's Respiratory Questionnaire (SGRQ) were applied to all patients. The number of patients that had a re-admission within 12 months was 246 (60.6%). Patients that had a re-admission had lower lung function and health status. A low forced expiratory volume in one second (FEV 1 ) and health status were independent predictors for re-admission. Hazard ratio (HR; 95% CI) was 0.82 (0.74–0.90) per 10% increase of the predicted FEV 1 and 1.06 (1.02–1.10) per 4 units increase in total SGRQ score. The risk of rehospitalisation was also increased in subjects with anxiety (HR 1.76 (1.16–2.68)) and in subjects with low health status (total SGRQ score &gt;60 units). When comparing the different subscales in the SGRQ, the closest relation between the risk of rehospitalisation was seen with the activity scale (HR 1.07 (1.03–1.11) per 4 unit increase). In patients with low health status, anxiety is an important risk factor for rehospitalisation. This may be important for patient treatment and warrants further studies.
Responsiveness of Preneoplastic and Neoplastic Mouse Mammary Tissues to Hormones: Casein and Histone Syntheses&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Philip Hohmann, Howard A. Bern, R. David Cole
Journal: JNCI Journal of the National Cancer Institute (1972)

Explants from 4 types of preneoplastic and neoplastic BALB/cCrgl mouse mammary tissues were tested for their ability to synthesize casein in vitro by incubation in a chemically defined medium containing insulin, cortisol, and prolactin, the hormone combination effective in the induction of casein synthesis in normal mammary tissue. One hyperplastic outgrowth (D1, of low tumorigenic potential) responded to these lactogenic hormones whereas a second (D2a, of high tumorigenic potential) did not, though both outgrowths were grossly similar morphologically. The tumors derived from D1 and D2a outgrowths were also unresponsive. The induction of casein in hyperplastic outgrowth D1 was accompanied by specific effects on the incorporation of lysine into individual lysine-rich histone subfractions that were qualitatively similar to those reported for normal tissue in vivo and in vitro. The hormones had no effects on the other 3 abnormal mammary tissues studied. Thus, the ability of the hormones to influence the metabolism of lysine-rich histone fractions was directly related to their ability to induce casein synthesis in the various tissues.