tbuckley/cabot-search huggingface dataset:
Cardiovascular effects of canrenone in patients with preascitic cirrhosis
Authors: Giorgio La Villa, Giuseppe Barletta, Roberto Giulio Romanelli, Giacomo Laffi, Riccarda Del Bene, Francesco Vizzutti, Pietro Pantaleo, Valeria Mazzocchi, Paolo Gentilini
Journal: Hepatology (2002)

In patients with cirrhosis and portal hypertension, standing induces a reduction in cardiac index (CI) and an increase in systemic vascular resistance index. Our previous studies indicate that this abnormal hemodynamic response to standing is due to an altered myocardial function, because cirrhotic patients are unable to compensate for the reduced preload with an increase in left ventricular (LV) ejection fraction (EF) and stroke volume. To evaluate whether the cardiac dysfunction in cirrhosis is influenced by canrenone, an aldosterone antagonist, 8 patients with preascitic, nonalcoholic cirrhosis, and portal hypertension underwent echocardiographic assessment of LV function and systemic hemodynamics and determinations of plasma volume, urinary sodium excretion, and plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (PNE) when on a 150-mmol/d-sodium diet (baseline), after 1 month on canrenone (100 mg/d) plus a 40-mmol/d-sodium diet and after 1 month on canrenone plus a 150-mmol/d-sodium diet. Echocardiographic evaluation was performed with the patient in the supine position and during active standing. At baseline, patients had high plasma volume and normal renal function, PRA, PAC, and PNE. CI, LVEF, and stroke volume index were also normal. Standing caused a significant reduction in CI and LVEF. After canrenone and either sodium diet, CI significantly decreased, and PRA and PNE increased in the supine position. On standing, LVEF and CI did not decrease further. Plasma volume significantly decreased only after low-sodium diet plus canrenone. In conclusion, canrenone normalizes the cardiac response to the postural challenge in patients with preascitic cirrhosis.
A painful liver
Authors: I Oliver
Journal: Gut (2004)

Background and aims: Gastric extranodal marginal zone B cell lymphoma of the mucosa associated lymphoid tissue (MALT)-type (MZBL) is a rare complication of Helicobacter pylori infection.Currently, no bacterial factor has been associated with the development of this disease.Our aim was to identify genes associated with lymphoma development.Methods: We used subtractive hybridisation as a tool for comparative genomics between H pylori strains isolated from a patient with gastric MZBL and from a patient with gastritis only.Results: When gastric MZBL strains were compared with gastritis strains, two open reading frames (ORFs) were significantly associated with gastric MZBL: JHP950 (74.4% v 48.7%, respectively; p = 0.023) and JHP1462 (25.6% v 2.6%, respectively; p = 0.004).The prevalence of JHP950 was 48.8% (p = 0.024) in duodenal ulcer strains and 39.3% (p = 0.006) in gastric adenocarcinoma strains, which makes this ORF a specific marker for gastric MZBL strains.In contrast, the prevalence of JHP1462 was 16% (p = 0.545) and 35.7% (p = 0.429) in duodenal ulcer and adenocarcinoma strains, respectively.These ORFs were present in reference strain J99 but not in reference strain 26695.JHP950 is located in the plasticity zone whereas the other, JHP1462, is located outside.Both encode for H pylori putative proteins with unknown functions.Conclusion: Despite its low prevalence, the ORF JHP1462 can be considered a candidate marker for H pylori strains involved in severe gastroduodenal diseases.In contrast, the ORF JHP950 has a high prevalence, and is the first candidate marker for strains giving rise to an increased risk of gastric MZBL strains.Further confirmation in other studies is needed.
Imaging Tumor Sensitivity to a Bioreductive Prodrug: Two for the Price of One!
Authors: J. Martin Brown
Journal: Clinical Cancer Research (2012)

Abstract Hypoxia is an important characteristic of many solid tumors and has a major negative effect on treatment response. A way to combat this effect is with drugs called “bioreductive prodrugs” or “hypoxic cytotoxins,” which are metabolized under hypoxia to toxic species. However, the patients with hypoxic tumors need to be identified. Clin Cancer Res; 18(6); 1487–9. ©2012 AACR.
The adenomatous polyposis coli tumour suppressor gene regulates c-<i>MYC</i> transcription in colon cancer cells
Authors: M Pignatelli
Journal: Gut (1999)

The adenomatous polyposis coli gene (APC) is a tumor suppressor gene that is inactivated in most colorectal cancers.Mutations of APC cause aberrant accumulation of -catenin, which then binds T cell factor-4 (Tcf-4), causing increased transcriptional activation of unknown genes.Here, the c-MYC oncogene is identified as a target gene in this signaling pathway.Expression of c-MYC was shown to be repressed by wild type APC and activated by -catenin, and these eVects were mediated through Tcf-4 binding sites in the c-MYC promoter.These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers.
Lifetime Risk for Diabetes Mellitus in the United States
Authors: K M Venkat Narayan, James P Boyle, Theodore J Thompson, Stephen W Sorensen, David F Williamson
Journal: JAMA (2003)

Although diabetes mellitus is one of the most prevalent and costly chronic diseases in the United States, no estimates have been published of individuals' average lifetime risk of developing diabetes.To estimate age-, sex-, and race/ethnicity-specific lifetime risk of diabetes in the cohort born in 2000 in the United States.Data from the National Health Interview Survey (1984-2000) were used to estimate age-, sex-, and race/ethnicity-specific prevalence and incidence in 2000. US Census Bureau data and data from a previous study of diabetes as a cause of death were used to estimate age-, sex-, and race/ethnicity-specific mortality rates for diabetic and nondiabetic populations.Residual (remaining) lifetime risk of diabetes (from birth to 80 years in 1-year intervals), duration with diabetes, and life-years and quality-adjusted life-years lost from diabetes.The estimated lifetime risk of developing diabetes for individuals born in 2000 is 32.8% for males and 38.5% for females. Females have higher residual lifetime risks at all ages. The highest estimated lifetime risk for diabetes is among Hispanics (males, 45.4% and females, 52.5%). Individuals diagnosed as having diabetes have large reductions in life expectancy. For example, we estimate that if an individual is diagnosed at age 40 years, men will lose 11.6 life-years and 18.6 quality-adjusted life-years and women will lose 14.3 life-years and 22.0 quality-adjusted life-years.For individuals born in the United States in 2000, the lifetime probability of being diagnosed with diabetes mellitus is substantial. Primary prevention of diabetes and its complications are important public health priorities.
Disrupting Polyamine Homeostasis as a Therapeutic Strategy for Neuroblastoma
Authors: Nicholas F. Evageliou, Michael D. Hogarty
Journal: Clinical Cancer Research (2009)

Abstract MYC genes are deregulated in a plurality of human cancers. Through direct and indirect mechanisms, the MYC network regulates the expression of &amp;gt; 15% of the human genome, including both protein-coding and noncoding RNAs. This complexity has complicated efforts to define the principal pathways mediating MYC's oncogenic activity. MYC plays a central role in providing for the bioenergetic and biomass needs of proliferating cells, and polyamines are essential cell constituents supporting many of these functions. The rate-limiting enzyme in polyamine biosynthesis, ODC, is a bona fide MYC target, as are other regulatory enzymes in this pathway. A wealth of data link enhanced polyamine biosynthesis to cancer progression, and polyamine depletion may limit the malignant transformation of preneoplastic lesions. Studies with transgenic cancer models also support the finding that the effect of MYC on tumor initiation and progression can be attenuated through the repression of polyamine production. High-risk neuroblastomas (an often lethal embryonal tumor in which MYC activation is paramount) deregulate numerous polyamine enzymes to promote the expansion of intracellular polyamine pools. Selective inhibition of key enzymes in this pathway, e.g., using DFMO and/or SAM486, reduces tumorigenesis and synergizes with chemotherapy to regress tumors in preclinical models. Here, we review the potential clinical application of these and additional polyamine depletion agents to neuroblastoma and other advanced cancers in which MYC is operative. (Clin Cancer Res 2009;15(19):5956–61)
Enhanced Activity of Hu14.18-IL2 Immunocytokine against Murine NXS2 Neuroblastoma when Combined with Interleukin 2 Therapy
Authors: Zane C. Neal, Jeannie C. Yang, Alexander L. Rakhmilevich, Ilia N. Buhtoiarov, Hillary E. Lum, Michael Imboden, Jacquelyn A. Hank, Holger N. Lode, Ralph A. Reisfeld, Stephen D. Gillies, Paul M. Sondel
Journal: Clinical Cancer Research (2004)

Abstract Established s.c. NXS2 murine neuroblastoma tumors exhibited transient resolution after suboptimal therapy using the hu14.18-IL2 immunocytokine (IC). The hu14.18-IL2 IC is a fusion protein that has linked a molecule of interleukin 2 (IL-2) to the COOH terminus of each of the IgG heavy chains on the humanized anti-GD2 monoclonal antibody hu14.18. To induce more potent and longer lasting in vivo antitumor effects, we tested hu14.18-IL2 IC in a regimen combining it with constant infusion IL-2 in NXS2 tumor-bearing mice. The addition of the constant infusion IL-2 augmented the antitumor response induced by treatment with the hu14.18-IL2 IC in animals with experimentally induced hepatic metastases and in animals bearing localized s.c. tumors. The combined treatment induced prolonged tumor eradication in most animals bearing s.c. tumors and involved both natural killer cells and T cells. The enhanced ability of this combined treatment to prevent tumor recurrence was not observed when a larger dose of hu14.18-IL2 IC, similar in IL-2 content to the IC plus systemic IL-2 regimen, was tested as single-agent therapy. Animals showing prolonged tumor eradication of established tumors after the combined hu14.18-IL2 plus IL-2 regimen exhibited a protective T-cell-dependent antitumor memory response against NXS2 rechallenge.
Diethylstilbestrol (DES) retains activity and is a reasonable option in patients previously treated with docetaxel for castration-resistant prostate cancer
Authors: C. Serrate, Y. Loriot, T. De La Motte Rouge, M. Gross-Goupil, C. Massard, B. Escudier, A. Bossi, K. Fizazi
Journal: Annals of Oncology (2009)
An ENU mutagenesis screen identifies novel and known genes involved in epigenetic processes in the mouse
Authors: Lucia Daxinger, Sarah K Harten, Harald Oey, Trevor Epp, Luke Isbel, Edward Huang, Nadia Whitelaw, Anwyn Apedaile, Anabel Sorolla, Joan Yong, Vandhana Bharti, Joanne Sutton, Alyson Ashe, Zhenyi Pang, Nathan Wallace, Daniel J Gerhardt, Marnie E Blewitt, Jeffrey A Jeddeloh, Emma Whitelaw
Journal: Genome biology (2013)

Abstract Background We have used a sensitized ENU mutagenesis screen to produce mouse lines that carry mutations in genes required for epigenetic regulation. We call these lines Modifiers of murine metastable epialleles ( Mommes ). Results We report a basic molecular and phenotypic characterization for twenty of the Momme mouse lines, and in each case we also identify the causative mutation. Three of the lines carry a mutation in a novel epigenetic modifier, Rearranged L-myc fusion ( Rlf ), and one gene, Rap-interacting factor 1 ( Rif1 ), has not previously been reported to be involved in transcriptional regulation in mammals. Many of the other lines are novel alleles of known epigenetic regulators. For two genes, Rlf and Widely-interspaced zinc finger ( Wiz ), we describe the first mouse mutants. All of the Momme mutants show some degree of homozygous embryonic lethality, emphasizing the importance of epigenetic processes. The penetrance of lethality is incomplete in a number of cases. Similarly, abnormalities in phenotype seen in the heterozygous individuals of some lines occur with incomplete penetrance. Conclusions Recent advances in sequencing enhance the power of sensitized mutagenesis screens to identify the function of previously uncharacterized factors and to discover additional functions for previously characterized proteins. The observation of incomplete penetrance of phenotypes in these inbred mutant mice, at various stages of development, is of interest. Overall, the Momme collection of mouse mutants provides a valuable resource for researchers across many disciplines.
Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome
Authors: Behzad Moghadaszadeh, Nathalie Petit, Céline Jaillard, Martin Brockington, Susana Quijano Roy, Luciano Merlini, Norma Romero, Brigitte Estournet, Isabelle Desguerre, Denys Chaigne, Francesco Muntoni, Haluk Topaloglu, Pascale Guicheney
Journal: Nature Genetics (2001)
Natural killer (NK) cell activity of peripheral blood, synovial fluid, and synovial tissue lymphocytes from patients with rheumatoid arthritis and juvenile rheumatoid arthritis.
Authors: J H Dobloug, O Forre, T K Kvien, T Egeland, M Degre
Journal: Annals of the Rheumatic Diseases (1982)

Natural killer (NK) cell activity was investigated in peripheral blood, synovial fluid, and synovial tissue lymphocytes from patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). Unfractionated lymphocytes, T lymphocytes, and non-T lymphocytes from the 3 compartments of JRA patients had reduced activity compared with that of normal peripheral blood lymphocytes (with p values usually between 0.05 and 0.1). Unfractionated synovial tissue lymphocytes of RA patients also showed reduced cytotoxicity (0.05 less than p less than 0.1), whereas peripheral blood lymphocytes exerted normal NK cell activity. The NK activity was exerted by cells both with and without Fc gamma receptors. The highest cytotoxicity was observed in Fc gamma receptor-positive cells, both in peripheral blood and synovial fluid, since more than 70% reduction in NK activity was found after depletion of Fc gamma receptor-positive cells. No evidence of lymphocytotoxic antibodies or other factors with influence on NK cells was observed in the patients9 sera.
Macrophage-Dependent Regulation of Syndecan Gene Expression
Authors: Jian Li, Lawrence F. Brown, Roger J. Laham, Rudiger Volk, Michael Simons
Journal: Circulation Research (1997)

Abstract Heparan sulfates in the extracellular matrix are required for a variety of biological processes, including cellular response to heparin-binding growth factors. However, little is known regarding the regulation of their expression and composition under pathophysiological conditions. In the present study, we have investigated the regulation of expression of two key heparan sulfate chain–carrying core proteins, syndecan-1 and syndecan-4, in a mouse/rat infarct model of tissue injury and repair. Induction of myocardial infarction was associated with a prompt increase in expression of both syndecan genes. Although infiltrating macrophages accounted for a substantial increase in syndecan expression, increased expression was noted in the levels of syndecan-1 mRNA in endothelial cells and syndecan-4 mRNA in cardiac myocytes. This increase in expression was limited to the immediate peri-infarct region and was absent from remote areas of the left or right ventricles. The influx of blood-derived macrophages in the heart correlated with the appearance of PR-39 peptide, which has previously been shown to increase syndecan expression in vitro. Studies in the op/op mice strain (which demonstrates sharply reduced levels of circulating monocytes) showed that myocardial infarction was associated with markedly reduced levels of macrophage influx and corresponding reduction in the expression of PR-39 and both syndecan genes. Pretreatment of op/op mice with granulocyte macrophage colony–stimulating factor restored myocardial macrophage content with corresponding restoration of PR-39/syndecan expression. In summary, myocardial infarction is associated with a distinct spatial and temporal pattern of syndecan-1 and -4 gene expression, which is induced by an influx of blood-derived macrophages.
Genetic Studies of Carcinogenesis in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: William S. Murray, Clarence C. Little
Journal: JNCI Journal of the National Cancer Institute (1967)

Data on seven reciprocal crosses involving five well-characterized inbred mouse stocks illustrate the reactions of physiologies produced by the various genomes to the presence or absence of the mammary fumor virus. Male transmission of the mammary tumor virus and its relation to the nodulogenic virus are discussed.
STUDIES ON THE IMMUNOTHERAPY OF RUNT DISEASE IN RATS
Authors: Willys K. Silvers, R. E. Billingham
Journal: The Journal of Experimental Medicine (1969)

Using rats of the Lewis and BN (Ag-B locus incompatible) isogenic strains, a comparative study has been made of the capacity to prevent or mitigate the development of runt disease with: (a) lymph node cell suspensions from normal adult BN rats, (b) node cells, or (c) serum from donors sensitized against Lewis tissue antigens, or (d) heterologous anti-lymphocyte serum (ALS) raised in rabbits against rat thymocytes. Following a standard intravenous or intraperitoneal inoculation of 20 x 10(6) Lewis node cells into neonatal BN hosts, there are cutaneous manifestations of runt disease within 11-15 days and death invariably takes place within 20 days. However, complete protection is afforded by administration of a similar number of normal BN node cells via a different vein, or admixed with the otherwise harmful Lewis node cells. However, timing of the administration was crucially important-precedence or delay by as little as 4 hr resulted in a great impairment of protection. When the inoculations of the two cell suspensions were separated by 24 hr, no protection was afforded. These and other observations suggested that a necessary condition for protection of the hosts by unsensitized isologous cells requires that they establish a prompt and intimate confrontation with the homologous target cells. At the same dosage level, suspensions of node cells from sensitized isologous donors were much more effective therapeutically, saving the lives of 92% of treated subjects when administered after a delay of 3 days, and of 19% when the delay was 4 or 5 days. Of the various immunotherapeutic agents studied, daily injections of 0.2 ml of isoantiserum gave the best results, and could totally reverse the course of the disease even when initiated at age 10-13 days and subjects already presented symptoms. ALS, although inferior to isoantiserum at the dosage levels tested, proved to be superior to sensitized isologous cells as a protective agent, since the initiation of daily injections after delays of 6 or 8 days were still effective. The observations that delayed treatments of infant rats with isoantisera or ALS resulted in complete recoveries sustain the thesis that the lesions responsible for the fatal outcome of runt diseases are not inflicted at a very early stage. The efficacy of both isoantisera and ALS as a means of inhibiting the progression of homologous disease also suggests that they may have therapeutic value in situations where this condition is encountered.
Mitogen-activated B-cell blasts reactive to more than one mitogen.
Authors: J Andersson, A Coutinho, F Melchers
Journal: The Journal of Experimental Medicine (1979)

One of three splenic B cells of 2- to 3-mo-old C57BL/6J or C3H/Tif mice are activated either by lipopolysaccharide (LPS) or by lipoprotein (LP) to grow and to mature to IgM-secreting cells. When mitogen-activated blast cells, after a 2-d activation period, are separated from nonactivated, small cells by velocity sedimentation, and no mitogen is readded, the blasts do not continue to grow but do continue to secrete IgM for several days. When the homologous mitogen is added for restimulation, the blast cells continue for several days to divide every 18 h and to develop IgM-secreting, plaque-forming cells. Frequency analyses at limiting dilutions of reactive B-blasts show that one cell in approximately equal to 1.2--1.5 blasts continue to grow and mature in the presence of the homologous mitogen, either LPS or LP. When the B-cell blasts obtained in a first activation period with either LPS or LP are restimulated with a heterologous mitogen, LPS, LP, Nocardia mitogen or mitogens contained in fetal calf serum a high proportion of the blasts continue to grow and mature to IgM-secreting cells. Frequency analyses show for LPS- or LP-blasts, restimulated in a heterologous fashion with either LP or LPS, that one cell in 1.35--1.5 blasts continue to divide and to mature to IgM-secreting cells. C3H/HeJ-splenic B-cells, which are LPS nonresponders, can only be activated to blast cells by LP. These LP-activated blasts can be restimulated by the homologous LP and by Nocardia mitogen and mitogens of fetal calf serum, but not by LPS. The results indicate that the majority of splenic B cells of 2- to 3-mo-old C57BL/6J or C3H/Tif mice are reactive to more than one B-cell mitogen. B cells, therefore, can possess in their surface membrane multireactive mitogen-receptor complexes which regulate growth and maturation.
Serotonin Transporter Distribution and Density in the Cerebral Cortex of Alcoholic and Nonalcoholic Comparison Subjects: A Whole-Hemisphere Autoradiography Study
Authors: Tuija Mantere, Erkki Tupala, Håkan Hall, Terttu Särkioja, Pirkko Räsänen, Kim Bergström, James Callaway, Jari Tiihonen
Journal: American Journal of Psychiatry (2002)

Lesions of the medial prefrontal cortex and dysfunctions in serotonin turnover are two well-established factors associated with impulsive and sociopathic behaviors, but no firm neuroanatomical data have linked these pathophysiological findings. The aims of this study were to identify putative areas in the human brain that are rich in serotonin transporter sites, particularly within the medial prefrontal cortex, and to determine whether serotonin transporter density in this area is altered among alcoholic subjects.Serotonin transporter density was measured among 17 alcoholic and 10 nonalcoholic comparison subjects by postmortem whole-hemisphere autoradiography with [(3)H]citalopram.In the human cerebral cortex, serotonin transporter binding sites were concentrated in the perigenual anterior cingulate cortex. Substantially sparser serotonin transporter density (up to 35%) was observed in the perigenual anterior cingulate cortex of alcoholic subjects in relation to nonalcoholic comparison subjects. After adjustment for age and postmortem delay, this finding remained statistically significant.A lower serotonin transporter density among the alcoholic subjects was observed, specifically in the so-called "affect" region, suggesting an association between ethanol addiction and dysfunctional serotonergic neurotransmission in this area.
The Crucial Role Of The Stratum Corneum Superficial Layers During Peanut Epicutaneous Immunotherapy (epit)
Authors: L. Mondoulet, V. Dioszeghy, M. Ligouis, V. Dhelft, E. Puteaux, C. Dupont, P. Benhamou
Journal: Journal of Allergy and Clinical Immunology (2011)