tbuckley/cabot-search huggingface dataset:
Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis
Authors: S Ardizzone
Journal: Gut (2005)

<b>Background and aim:</b> There are limited evidence based data concerning the use of azathioprine in ulcerative colitis. We aimed to compare the efficacy of azathioprine and oral 5-aminosalicylic acid in inducing remission of steroid dependent ulcerative colitis. <b>Methods:</b> Seventy two patients with steroid dependent ulcerative colitis were admitted to this investigator-blind study. Steroid dependence was defined as a requirement for steroid therapy ⩾10 mg/day during the preceding six months, with at least two attempts to discontinue the medication. The disease had to be clinically and endoscopically active at study entry, and all patients were taking systemic prednisolone (40 mg/day). Patients were randomised to receive azathioprine 2 mg/kg/day or oral 5-aminosalicylic acid 3.2 g/day, for a six month follow up period. The outcome of the treatment was defined as (1) success, indicating induction of clinical and endoscopic remission and steroid discontinuation, or (2) failure, indicating the absence of clinical and endoscopic remission and therefore the need for at least one further cycle of systemic steroids to control symptoms, apart from the initial one, or colectomy. <b>Results:</b> Significantly more patients in the azathioprine than in the 5-aminosalicylic acid group had clinical and endoscopic remission, and discontinued steroid therapy, both in the intention to treat (azathioprine <i>v</i> 5-aminosalicylic acid: 19/36 patients (53%) <i>v</i> 7/36 (21%); odds ratio (OR) 4.78 (95% confidence interval (CI) 1.57–14.5)) and per protocol (azathioprine <i>v</i> 5-aminosalicylic acid: 19/33 patients (58%) <i>v</i> 7/34 (21%); OR 5.26 (95% CI 1.59–18.1)) analysis. <b>Conclusions:</b> Azathioprine is significantly more effective than 5-aminosalicylic acid in inducing clinical and endoscopic remission and avoiding steroid requirement in the treatment of steroid dependent ulcerative colitis.
Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro.
Authors: R L Barbieri, J Gochberg, K J Ryan
Journal: Journal of Clinical Investigation (1986)

Epidemiologic studies suggest that women who smoke have lower endogenous estrogen than nonsmokers. To explore the possible link between cigarette smoking and decreased endogenous estrogens, we have examined the effects of constituents of tobacco on estrogen production in human choriocarcinoma cells and term placental microsomes. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase. In the choriocarcinoma cell cultures, a supraphysiologic concentration of androstenedione (73 microM) in the culture medium blocked the inhibition of aromatase caused by nicotine, cotinine, and anabasine. In preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.
The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity
Authors: Jun-ichi Hanai, Peirang Cao, Preeti Tanksale, Shintaro Imamura, Eriko Koshimizu, Jinghui Zhao, Shuji Kishi, Michiaki Yamashita, Paul S. Phillips, Vikas P. Sukhatme, Stewart H. Lecker
Journal: Journal of Clinical Investigation (2007)

Statins inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis, and are widely used to treat hypercholesterolemia. These drugs can lead to a number of side effects in muscle, including muscle fiber breakdown; however, the mechanisms of muscle injury by statins are poorly understood. We report that lovastatin induced the expression of atrogin-1, a key gene involved in skeletal muscle atrophy, in humans with statin myopathy, in zebrafish embryos, and in vitro in murine skeletal muscle cells. In cultured mouse myotubes, atrogin-1 induction following lovastatin treatment was accompanied by distinct morphological changes, largely absent in atrogin-1 null cells. In zebrafish embryos, lovastatin promoted muscle fiber damage, an effect that was closely mimicked by knockdown of zebrafish HMG-CoA reductase. Moreover, atrogin-1 knockdown in zebrafish embryos prevented lovastatin-induced muscle injury. Finally, overexpression of PGC-1α, a transcriptional coactivator that induces mitochondrial biogenesis and protects against the development of muscle atrophy, dramatically prevented lovastatin-induced muscle damage and abrogated atrogin-1 induction both in fish and in cultured mouse myotubes. Collectively, our human, animal, and in vitro findings shed light on the molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be a critical mediator of the muscle damage induced by statins.
DNA damage-induced cellular senescence is sufficient to suppress tumorigenesis: a mouse model
Authors: Thang Van Nguyen, Nahum Puebla-Osorio, Hui Pang, Melanie E. Dujka, Chengming Zhu
Journal: The Journal of Experimental Medicine (2007)

Tumor suppressor p53-dependent apoptosis is critical in suppressing tumorigenesis. Previously, we reported that DNA double-strand breaks (DSBs) at the V(D)J recombination loci induced genomic instability in the developing lymphocytes of nonhomologous end-joining (NHEJ)–deficient, p53-deficient mice, which led to rapid lymphomagenesis. To test the ability of p53-dependent cell cycle arrest to suppress tumorigenesis in the absence of apoptosis in vivo, we crossbred NHEJ-deficient mice into a mutant p53R172P background; these mice have defects in apoptosis induction, but not cell cycle arrest. These double-mutant mice survived longer than NHEJ/p53 double-null mice and, remarkably, were completely tumor free. We detected accumulation of aberrant V(D)J recombination–related DSBs at the T cell receptor (TCR) locus, and high expression levels of both mutant p53 and cell cycle checkpoint protein p21, but not the apoptotic protein p53-upregulated modulator of apoptosis. In addition, a substantial number of senescent cells were observed among both thymocytes and bone marrow cells. Cytogenetic studies revealed euploidy and limited chromosomal breaks in these lymphoid cells. The results indicate that precursor lymphocytes, which normally possess a high proliferation potential, are able to withdraw from the cell cycle and undergo senescence in response to the persistence of DSBs in a p53–p21–dependent pathway; this is sufficient to inhibit oncogenic chromosomal abnormality and suppress tumorigenesis.
KAPOSI'S IDIOPATHIC SARCOMA IS NOT A GENUINE SARCOMA BUT A NEUROVASCULAR DYSGENESIS
Authors: L. M. PAUTRIER, A. DISS
Journal: British Journal of Dermatology (1929)

Journal Article KAPOSI'S IDIOPATHIC SARCOMA IS NOT A GENUINE SARCOMA BUT A NEUROVASCULAR DYSGENESIS Get access L. M. PAUTRIER, L. M. PAUTRIER Clinic for Shin Diseases of the Faculty of Medicine of Strasbourg Search for other works by this author on: Oxford Academic Google Scholar A. DISS A. DISS Clinic for Shin Diseases of the Faculty of Medicine of Strasbourg Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 41, Issue 3, 1 March 1929, Pages 93–105, https://doi.org/10.1111/j.1365-2133.1929.tb09319.x Published: 01 March 1929
Tracing Biological Collections
Authors: Francine Kauffmann, Anne Cambon-Thomsen
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Helping Patients Make Informed Choices: A Randomized Trial of a Decision Aid for Adjuvant Chemotherapy in Lymph Node-Negative Breast Cancer
Authors: T. Whelan, C. Sawka, M. Levine, A. Gafni, L. Reyno, A. Willan, J. Julian, S. Dent, H. Abu-Zahra, E. Chouinard, R. Tozer, K. Pritchard, I. Bodendorfer
Journal: JNCI Journal of the National Cancer Institute (2003)

In recent years, patients have indicated a desire for more information about their disease and to be involved in making decisions about their care. We developed an aid called the "Decision Board" to help clinicians inform patients with lymph node-negative breast cancer of the risks and benefits of adjuvant chemotherapy. We determined whether adding the Decision Board to the medical consultation improved patient knowledge and satisfaction compared with the medical consultation alone.Between October 1995 and March 2000, 176 women with lymph node-negative breast cancer who were candidates for adjuvant chemotherapy were randomly assigned to receive the Decision Board plus the medical consultation (83 patients) or the medical consultation alone (93 patients). One week after the consultation, patients completed a questionnaire assessing their knowledge about breast cancer and chemotherapy. Satisfaction with decision making was assessed 1 week and 3, 6, and 12 months after randomization, and differences between groups were analyzed by a repeated measures analysis of variance. All statistical tests were two-sided.Patients in the Decision Board arm were better informed about breast cancer and adjuvant chemotherapy than patients in the control arm (mean knowledge score = 80.2 [on a scale of 0-100], 95% confidence interval [CI] = 77.1 to 83.3, and 71.7, 95% CI = 69.0 to 74.4, respectively; P<.001). Over the entire study period, satisfaction with decision making was higher for patients in the Decision Board arm than for patients in the control arm (P =.032). There was no statistically significant difference between the two groups in the number of patients who chose adjuvant chemotherapy (77% and 70% for patients in the Decision Board arm and those in the control arm, respectively; P =.303).When making decisions regarding adjuvant chemotherapy, patients with early breast cancer who had been exposed to the Decision Board had better knowledge of the disease and treatment options and greater satisfaction with their decision making than those who received the standard consultation.
Hutchinson Smoking Prevention Project: Long-Term Randomized Trial in School-Based Tobacco Use Prevention--Results on Smoking
Authors: A. V. Peterson
Journal: JNCI Journal of the National Cancer Institute (2000)

No long-term impact has yet been observed with the use of the social-influences approach to school-based smoking prevention for youth. However, whether this lack of impact is due to methodologic problems with the studies or to the failure of the interventions is unclear. The Hutchinson Smoking Prevention Project (HSPP), conducted from September 1984 through August 1999, aimed to attain the most rigorous randomized trial possible to determine the long-term impact of a theory-based, social-influences, grade 3-12 intervention on smoking prevalence among youth.Forty Washington school districts were randomly assigned to the intervention or to the control condition. Study participants were children enrolled in two consecutive 3rd grades in the 40 districts (n = 8388); they were followed to 2 years after high school. The trial achieved high implementation fidelity and 94% follow-up. Data were analyzed with the use of group-permutation methods, and all statistical tests were two-sided.No significant difference in prevalence of daily smoking was found between students in the control and experimental districts, either at grade 12 (difference [Delta] = 0.2%, 95% confidence interval [CI] = -4.6% to 4.4%, and P =.91 for girls; Delta = 0.3%, 95% CI = -5.0% to 5.5%, and P =.89 for boys) or at 2 years after high school (Delta = -1.4%, 95% CI = -5.0% to 1.6%, and P =.38 for girls; Delta = 2.6%, 95% CI = -2.5% to 7.7%, and P =.30 for boys). Moreover, no intervention impact was observed for other smoking outcomes, such as extent of current smoking or cumulative amount smoked, or in subgroups that differ in a priori specified variables, such as family risk for smoking.The rigor of the HSPP trial suggests high credence for the intervention impact results. Consistent with previous trials, there is no evidence from this trial that a school-based social-influences approach is effective in the long-term deterrence of smoking among youth.
Renal metabolism of amino acids and ammonia in subjects with normal renal function and in patients with chronic renal insufficiency.
Authors: A Tizianello, G De Ferrari, G Garibotto, G Gurreri, C Robaudo
Journal: Journal of Clinical Investigation (1980)

The net renal metabolism of amino acids and ammonia in the post absorptive state was evaluated in subjects with normal renal function and in patients with chronic renal insufficiency by measuring renal uptake and release, and urinary excretion of free amino acids and ammonia. In normal subjects the kidney extracts glutamine, proline, citrulline, and phenylalanine and releases serine, arginine, taurine, threonine, tyrosine, ornithine, lysine, and perhaps alanine. The renal uptake of amino acids from arterial blood occurs by way of plasma only, whereas approximately a half of amino acid release takes place by way of blood cells. Glycine is taken up from arterial plasma, while similar amounts of this amino acid are released by way of blood cells. In the same subjects total renal ammonia production can be largely accounted for by glutamine extracted. In patients with chronic renal insufficiency (a) the renal uptake of phenylalanine and the release of taurine and ornithine disappear; (b) the uptake of glutamine and proline, and the release of serine and threonine are reduced by 80--90%; (c) the uptake of citrulline and the release of alanine, arginine, tyrosine, and lysine are reduced by 60--70%; (d) no exchange of glycine is detectable either by way of plasma or by way of blood cells; (e) exchange of any other amino acid via blood cells disappears, and (f) total renal ammonia production is reduced and not more than 35% of such production can be accounted for by glutamine extracted, so that alternative precursors must be used. A 140% excess of nitrogen release found in the same patients suggests an intrarenal protein and peptide breakdown, which eventually provides free amino acids for ammonia production.
ENTEROVIRAL RIBONUCLEIC ACID
Authors: John J. Holland, Bill H. Hoyer, Leroy C. McLaren, Jerome T. Syverton
Journal: The Journal of Experimental Medicine (1960)

A relatively sensitive and adequately reproducible assay of infectious enteroviral RNA was obtained by exposing calf serum-grown HeLa cells to RNA suspended in 2 M magnesium sulfate solution. Highly purified enteroviral preparations yielded RNA exhibiting more than 0.1 per cent of the infectivity of whole original virus and infectivity regressed linearly with dilution. Radioisotope experiments with P32-labeled RNA and spectrophotometric studies demonstrated that Gierer-Schramm phenol extraction permits almost quantitative recovery of high molecular weight RNA from poliovirus. Intact chromatography-purified type 2 poliovirus in the analytical ultracentrifuge showed a sharp boundary and a sedimentation coefficient of S20, w = 147 ± 5S. Phenol-extracted poliovirus RNA exhibited a heterodisperse sedimentation pattern with a large proportion of homogeneous, rapidly sedimenting material having a coefficient of S20, w = 37 ± 2S. Although the bulk of extracted poliovirus RNA as measured by radiophosphorus labeling was not taken up by cells, the infectious fraction of RNA was adsorbed rapidly by HeLa-cell or L strain mouse fibroblast monolayers, indicating a possible dissimilarity between the bulk of extracted virus RNA and a relatively small fraction responsible for infectivity. Enhancement of poliovirus RNA infectivity for HeLa cells by high ionic-strength magnesium sulfate solution appeared due partly to an effect of hypertonicity on cells, and partly to an effect of high-concentration divalent cation on RNA itself, but not to enhancement of adsorption. Poliovirus RNA adsorbed by HeLa cells apparently was rapidly received within the cells since it became quickly insusceptible to ribonuclease. Heterologous nucleic acids and degradation products to the level of oligoribonucleotides inhibited infectivity of poliovirus RNA for HeLa cells. This inhibitory activity appeared due to intermolecular complexing, since exposure of cells to heterologous RNA immediately before or after exposure to virus RNA failed to reduce infectivity. Ultraviolet absorption spectra demonstrated that the RNA within intact poliovirus is more hypochromic (and thus more extensively hydrogen-bonded) than is the same RNA isolated by phenol extraction, and suspended in 0.02 M phosphate buffer.
Alterations of lung structure in experimental diabetes, and diabetes associated with hyperlipidaemia in hamsters
Authors: D Popov, M Simionescu
Journal: European Respiratory Journal (1997)

Since hyperglycaemia is known to affect normal pulmonary physiology and biochemistry and few structure-function correlations have been reported, we designed experiments on hamsters subjected to streptozotocin-induced diabetes or diabetes associated with hyperlipidaemia, and investigated the impact of these conditions on the lung structure. At time intervals ranging 2-24 weeks from the inception of disease (without correcting blood glucose with insulin), the animals were sacrificed, and plasma glucose and cholesterol assayed. The lung was processed for electron microscopy, and the structural changes of the capillary and venular endothelium, of epithelial cells, and interstitium were examined. In diabetic animals, especially after 6 weeks of disease, a gradual narrowing of approximately 35% of the capillaries and approximately 30% of the alveoli, and hyperplasia of the extracellular matrix, rich in collagen bundles, were observed. Frequently, capillaries contained adherent intravascular macrophages suggestive of an inflammatory process. The capillary endothelium was characterized by numerous plasmalemmal vesicles, often fused, well-developed synthesizing apparatus (endoplasmic reticulum and Golgi complex) and cytoskeleton, and an uneven distribution of the anionic sites on the luminal plasmalemma. The venular endothelium was particularly rich in Weibel-Palade bodies. The alveolar epithelium was often collapsed, compressing surfactant within the airspace. The lung interstitium was apparently enlarged, and the fibroblasts and contractile interstitial cells frequently contained lipid droplets. These alterations were more pronounced and occurred at a faster rate (4 weeks) in diabetes associated with hyperlipidaemia. The structural modifications reported in this study support the functional disturbances observed in association with hyperglycaemia, sustaining the conclusion that the lung is an organ affected by diabetes.
Evolutionary Dynamics of Introns in Plastid-Derived Genes in Plants: Saturation Nearly Reached but Slow Intron Gain Continues
Authors: M. K. Basu, I. B. Rogozin, O. Deusch, T. Dagan, W. Martin, E. V. Koonin
Journal: Molecular Biology and Evolution (2007)

Some of the principal transitions in the evolution of eukaryotes are characterized by engulfment of prokaryotes by primitive eukaryotic cells. In particular, approximately 1.6 billion years ago, engulfment of a cyanobacterium that became the ancestor of chloroplasts and other plastids gave rise to Plantae, the major branch of eukaryotes comprised of glaucophytes, red algae, green algae, and green plants. After endosymbiosis, there was large-scale migration of genes from the endosymbiont to the nuclear genome of the host such that approximately 18% of the nuclear genes in Arabidopsis appear to be of chloroplast origin. To gain insights into the process of evolution of gene structure in these, originally, intronless genes, we compared the properties and the evolutionary dynamics of introns in genes of plastid origin and ancestral eukaryotic genes in Arabidopsis, poplar, and rice genomes. We found that intron densities in plastid-derived genes were slightly but significantly lower than those in ancestral eukaryotic genes. Although most of the introns in both categories of genes were conserved between monocots (rice) and dicots (Arabidopsis and poplar), lineage-specific intron gain was more pronounced in plastid-derived genes than in ancestral genes, whereas there was no significant difference in the intron loss rates between the 2 classes of genes. Thus, after the transfer to the nuclear genome, the plastid-derived genes have undergone a massive intron invasion that, by the time of the divergence of dicots and monocots (150-200 MYA), yielded intron densities only slightly lower than those in ancestral genes. Nevertheless, the accumulation of introns in plastid-derived genes appears not to have reached saturation and continues to this time, albeit at a low rate. The overall pattern of intron gain and loss in the plastid-derived genes is shaped by this continuing gain and the more general tendency for loss that is characteristic of the recent evolution of plant genes.
Metabolism of orally administered cadmium-metallothionein in mice.
Authors: M G Cherian
Journal: Environmental Health Perspectives (1979)

The main source of cadmium in the diet is cereal or meat, especially in liver and kidney. Since the cadmium in both liver and kidney is bound to metallothionein, a heat-stable protein, the gastrointestinal absorption and metabolism of cadmium metallothionein (CdMt) was studied in detail. The selective renal cadmium deposition after oral CdMt was analogous to the studies on injected CdMt. Metallothionein with 109Cd or 35S-cysteine radioactive label was isolated from rat liver and administered orally (60 microgram Cd) through a gastric tube to mice (C57 BL/6J). After 4 hr, a major portion of the ingested CdMt was isolated intact from intestinal mucosal cells. However, only a small amount of cadmium bound metallothionein was present in the kidney supernatant. The protein moeity was also degraded completely in kidney. The absorption and tissue distribution of cadmium from oral-cysteine and cadmium-glutathione complexes were similar to that after oral CdCl2 in mice. These results that oral CdMt may be absorbed intact from the gastrointestinal tract and the protein is degraded during renal deposition.