tbuckley/cabot-search huggingface dataset:
Population-Based Risks of CNS Tumors in Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study
Authors: Aliki J. Taylor, Mark P. Little, David L. Winter, Elaine Sugden, David W. Ellison, Charles A. Stiller, Marilyn Stovall, Clare Frobisher, Emma R. Lancashire, Raoul C. Reulen, Michael M. Hawkins
Journal: Journal of Clinical Oncology (2010)

Purpose CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in Britain, but the relationship of risk to doses of previous radiotherapy and chemotherapy is uncertain. Methods The British Childhood Cancer Survivor Study is a national, population-based, cohort study of 17,980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national, population-based cancer registries identified 247 SPNs of the CNS. Cohort and nested case-control studies were undertaken. Results There were 137 meningiomas, 73 gliomas, and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly, and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01 to 9.99, 10.00 to 19.99, 20.00 to 29.99, 30.00 to 39.99 and ≥ 40 Gy had risks that were two-fold, eight-fold, 52-fold, 568-fold, and 479-fold, respectively, the risks experienced by those whose meningeal tissue was unexposed. The risk of meningioma among individuals receiving 1 to 39,40 to 69, and at least 70 mg/m 2 of intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the risk experienced by those unexposed. The standardized incidence ratio for gliomas was 10.8 (95% CI, 8.5 to 13.6). The risk of glioma/primitive neuroectodermal tumors increased linearly with dose of radiation, and those who had CNS tissue exposed to at least 40 Gy experienced a risk four-fold that experienced by those who had CNS tissue unexposed. Conclusion The largest-ever study, to our knowledge, of CNS tumors in survivors of childhood cancer indicates that the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and with increased dose of intrathecal methotrexate.
NSAIDs: the Emperor's new dogma?
Authors: I Bjarnason
Journal: Gut (2003)

The spectacular marketing success of the selective cyclooxygenase 2 (COX-2) inhibitors is largely based on efficacy comparable with conventional non-steroidal anti-inflammatory drugs (NSAIDs) with vastly improved gastrointestinal safety. The additional key to the marketing success is the purity and simplicity of the message—that is, COX-1 inhibition causes the gastrointestinal side effects of NSAIDs (COX-1 dogma) while COX-2 blocking confers the therapeutic benefits (COX-2 dogma). Adherence to the COX dogmas with development of COX-2 selective agents has undoubtedly benefited many patients, but ironically their scientific basis is now seriously challenged by experimentation.
Safety of 10 days ticlopidine after coronary stenting — a randomized comparison with 30 days: Strategic AL ternatives with T iclopidine in S tenting study (SALTS)
Authors: G.Y.F. Szto, T.J. Linnemeier, S.J. Lewis, K.K. Punamiya, S.C. Jung, D.A. Rothbaum, R.J. Landin, M.W. Ball, R.V. Riddell, Z.I. Hodes, D.L. Lips, G.B. Elsner, M. Potrikus, J.L. Coverdale
Journal: Journal of the American College of Cardiology (1998)
Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience
Authors: Claire Alapetite, Herve Brisse, Catherine Patte, Marie Anne Raquin, Genevieve Gaboriaud, Christian Carrie, Jean Louis Habrand, Philippe Thiesse, Jean Claude Cuilliere, Valerie Bernier, M. Ben-Hassel, Didier Frappaz, Marie Christine Baranzelli, Eric Bouffet
Journal: Neuro-Oncology (2010)

Over the last two decades, chemotherapy has been introduced in protocols for patients with intracranial germinoma with the objective of reducing the volume and the dose of irradiation without compromising survival rates. The aim of this work is to critically analyze the pattern of relapse in a cohort of patients with nonmetastatic germinoma prospectively treated with chemotherapy followed by focal field radiation. Data of all germinoma patients registered in the French protocol for intracranial germ cell tumors between 1990 and 1999 were reviewed. The pattern of relapse, management, and outcome were analyzed in 10 of 60 patients who developed a recurrence after initial treatment. In 9 patients, the site of recurrence was local or loco-regional, notably in the periventricular area for 8. One patient only had isolated distant leptomeningeal relapse. The review of the sites of relapse suggests that most recurrences could have been avoided with a larger ventricular field of radiation. Treatment at first relapse included chemotherapy (10 patients), high-dose chemotherapy and stem cell transplant (8 patients), and/or radiation therapy (4 patients). Five patients experienced a second relapse. At a median follow-up of 72 months since the first relapse, 8 patients are alive in second or third remission. This review identified an excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma. These relapses are predominantly marginal or outside radiation fields. Ventricular field radiation appears a logical alternative to decrease the incidence of such relapses. Future trials should aim at better identifying patients who may benefit from local and ventricular radiation, respectively.
Oxidative Stress Causes Renal Dopamine D1 Receptor Dysfunction and Hypertension via Mechanisms That Involve Nuclear Factor-κB and Protein Kinase C
Authors: Anees Ahmad Banday, Fatima Rizwan Fazili, Mustafa F. Lokhandwala
Journal: Journal of the American Society of Nephrology (2007)

Renal dopamine, via activation of D1 receptors, plays a role in maintaining sodium homeostasis and BP. There exists a defect in renal D1 receptor function in hypertension, diabetes, and aging, conditions that are associated with oxidative stress. However, the exact underlying mechanism of the oxidative stress-mediated impaired D1 receptor signaling and hypertension is not known. The effect of oxidative stress on renal D1 receptor function was investigated in healthy animals. Male Sprague-Dawley rats received tap water (vehicle) and 30 mM L-buthionine sulfoximine (BSO), an oxidant, with and without 1 mM tempol for 2 wk. Compared with vehicle, BSO treatment caused oxidative stress and increase in BP, which was accompanied by defective D1 receptor G-protein coupling and loss of natriuretic response to SKF38393. BSO treatment also increased NF-kappaB nuclear translocation, protein kinase C (PKC) activity and expression, G-protein-coupled receptor kinase-2 (GRK-2) membranous translocation, and D1 receptor serine phosphorylation. In BSO-treated rats' supplementation of tempol decreased oxidative stress, normalized BP, and restored D1 receptor G-protein coupling and natriuretic response to SKF38393. Tempol also normalized NF-kappaB translocation, PKC activity and expression, GRK-2 sequestration, and D1 receptor serine phosphorylation. In conclusion, these results show that oxidative stress activates NF-kappaB, causing an increase in PKC activity, which leads to GRK-2 translocation and subsequent D1 receptor hyper-serine phosphorylation and uncoupling. The functional consequence of this phenomenon was the inability of SKF38393 to inhibit Na/K-ATPase activity and promote sodium excretion, which may have contributed to increase in BP. Tempol reduced oxidative stress and thereby restored D1 receptor function and normalized BP.
Requirement of Gab2 for mast cell development and KitL/c-Kit signaling
Authors: Keigo Nishida, Lin Wang, Eiichi Morii, Sung Joo Park, Masahiro Narimatsu, Shousaku Itoh, Satoru Yamasaki, Masahiro Fujishima, Katsuhiko Ishihara, Masahiko Hibi, Yukihiko Kitamura, Toshio Hirano
Journal: Blood (2002)
Mitochondrial DNA polymorphisms in subterranean mole-rats of the Spalax ehrenbergi superspecies in Israel, and its peripheral isolates.
Authors: E Nevo, R L Honeycutt, H Yonekawa, K Nelson, N Hanzawa
Journal: Molecular Biology and Evolution (1993)

Patterns of mitochondrial DNA (mtDNA) variation were examined in 133 mole-rats constituting all four chromosomal species (2n = 52, 2n = 54, 2n = 58, and 2n = 60) of the Spalax ehrenbergi superspecies in Israel, as well as the peripheral isolates of 2n = 60. In the main range of the complex, a total of 28 mtDNA haplotypes were found in 64 mole-rats, with most haplotypes being unique to either a single chromosomal species or population. mtDNA divergence increased from low to high diploid number in a north-to-south direction in Israel. Overall levels of mtDNA diversity were unexpectedly the highest in the 2n = 60, the youngest species of the complex. The mtDNA haplotypes can be separated into two major groups, 2n = 52-54 and 2n = 58-60, and a phylogenetic analysis for each group revealed evidence of a few haplotypes not sorted by diploid number. The overall patterns of mtDNA divergence seen within and among the four chromosomal species are consistent with the parapatric mode of speciation as suggested from previous studies of allozyme and DNA hybridization. In a separate data set the patterns of mtDNA variation were examined across the main geographic range and across peripheral semi-isolates and isolates of the 2n = 60 chromosomal species. Fifteen haplotypes were found in 69 mole-rats. High levels of mtDNA diversity characterized the main range, semi-isolated, and even some desert isolated populations. The peripheral isolates contain much mtDNA diversity, including novel haplotypes.
Chronological expression of Ciliated Bronchial Epithelium 1 during pulmonary development
Authors: H. M. Haitchi, H. Yoshisue, A. Ribbene, S. J. Wilson, J. W. Holloway, F. Bucchieri, N. A. Hanley, D. I. Wilson, G. Zummo, S. T. Holgate, D. E. Davies
Journal: European Respiratory Journal (2009)

<i>Ciliated Bronchial Epithelium</i> (<i>CBE</i>) <i>1</i> is a novel gene, which is expressed in ciliated cells. As cilia are important during embryogenesis, the present authors characterised the murine homologue of <i>CBE1</i> (<i>Cbe1</i>) and compared its temporal expression during murine and human lung development. <i>Cbe1</i> cDNA was cloned and characterised using sequencing, standard PCR and Western blotting. Mouse and human embryonic/fetal lungs (HELs) were harvested for mRNA analysis and protein localisation <i>in vivo</i> and <i>in vitro</i> using RT-PCR and immunohistochemistry. The Cbe1 amino acid sequence was &gt;75% identical with CBE1 and its alternative splicing and tissue distribution were highly conserved. Pulmonary expression of <i>Cbe1</i> mRNA was increased at embryonic day (E)16, 1 day later than <i>Foxj1</i>, which is consistent with a role in ciliogenesis. In HELs, <i>CBE1</i> mRNA was detectable at 8–9 weeks post-conception and increased in explant culture. CBE1 protein expression was weak at 10 weeks post-conception but strong at 12.3 weeks post-conception, in parallel with cilia formation. Additionally, <i>Cbe1</i> mRNA was expressed at E11 (4–5 weeks post-conception in HELs) in the absence of <i>Foxj1</i>, implying a distinct role in early development. Chronological regulation of <i>CBE1/Cbe1</i> expression during pulmonary differentiation suggests involvement in ciliogenesis, with an additional role during early lung development.
Psoriasis patients have highly increased numbers of tryptase-positive mast cells in the duodenal stroma
Authors: G. ICHAËLSSON, W. KRAAZ, E. HAGFORSEN, I. PIHL-LUNDIN, L. LÖÖF
Journal: British Journal of Dermatology (1997)

We have shown that the number of tryptase-positive mast cells in the duodenal mucosa in psoriasis is increased and that a subgroup of psoriasis patients showed elevated levels of antibodies to gliadin (some of whom also had increased lymphocytes in the duodenal epithelium). Duodenal biopsy specimens from 37 patients with psoriasis (eight mild, 13 moderate and 16 severe) and 22 patients with irritable bowel syndrome (IBS) were examined regarding the presence of tryptase + mast cells. Intraepithelial infiltration by lymphocytes was evaluated and scored from 0 to 3. Patients with psoriasis had 131 +/- 58 mast cells/mm2 (mean +/- SD) and those with IBS 28 +/- 18. Only in four of the 37 psoriasis patients was the number within the range of that in the IBS group. There were no signs of stromal inflammation except in one psoriasis patient. No relationship was found between degree of severity of psoriasis and number of mast cells. In 25 of the 37 specimens from psoriasis patients there was no increase in intraepithelial lymphocytes, whereas seven showed a slight increase (score 1-2) and five a moderate increase (score > or = 2-3). The number of tryptase + mast cells was similar in patients with or without increased intraepithelial lymphocytes. The number of mast cells showed no relation to the presence or absence of antibodies to gliadin. We hypothesize that there are at least two types of abnormalities in the duodenal mucosa in psoriasis, one type that is present in most psoriasis patients and characterized by an increase in mast cells and eosinophils, and another that is present in a subgroup of patients with antibodies to gliadin and an increased number of duodenal intraepithelial lymphocytes. The mechanisms underlying the increase in the number of mast cells and its relevance are not yet known.
Selective potentiation of insulin-mediated glucose disposal in normal dogs by the sulfonylurea glipizide.
Authors: W S Putnam, D K Andersen, R S Jones, H E Lebovitz
Journal: Journal of Clinical Investigation (1981)

Investigative data have suggested that the extrapancreatic actions of the sulfonylureas may be paramount in their chronic antidiabetic action. The present study examines the effects of chronic sulfonylurea treatment on in vivo insulin action. Peripheral insulin levels, hepatic glucose production (Ra), and overall glucose disposal (Rd) were studied in six awake, normal dogs given both 0.5 and 1.0 mU/kg per min pork insulin for 2.5 h. This produces stable hyperinsulinemia from 15 to 150 min. Fasting euglycemia was held constant by the glucose clamp technique and averaged 99% basal glucose in all studies. Ra and Rd were determined from infusion of [3-(3)H]glucose, begun 90 min prior to insulin infusion. 10 mg of the sulfonylurea glipizide, was given daily to the test animals for the 10 to 20 d following appropriate control studies, then was withheld for 24 h, and the dogs were restudied. Glipizide treatment did not significantly alter basal glucose turnover, Ra, mean glucose values, or mean insulin levels as determined by radioimmunoassay. Increase in Rd above basal glucose turnover in response to insulin (delta Rd) was significantly (P less than 0.05) increased by glipizide treatment at both insulin dosage levels (paired analysis). At 1.0 mU/kg per min insulin, delta Rd rose from 2.6 mg/kg per min before glipizide to 6.5 mg/kg per min after glipizide treatment. At 0.5 mU/kg per min insulin, delta Rd went from 1.1 mg/kg per min before glipizide to 2.2 mg/kg per min after glipizide treatment. Glipizide treatment doubled the effects of insulin on Rd, while showing no significant effect upon insulin suppression of Ra. We conclude that a significant extrapancreatic chronic action of glipizide lies in its ability to selectively potentiate Rd.
DNA flow cytometry on human epidermis. The effect of serial biopsy sampling at various times
Authors: GERDA FRENTZ, ULLA MoLLER, N. KEIDING
Journal: British Journal of Dermatology (1982)

The effect of serial biopsy sampling on S- and G2 + M-fractions in lower abdominal skin from leg ulcer patients was studied by single-nuclei DNA flow cytometry. Significant differences in both measurements were found in four biopsies taken at equal intervals within 24 h, but not in four biopsies taken at noon on four consecutive days. The variation in S-fractions was closely related to the injury from previous biopsy sampling(s) while the G3 + M-fraction variation tended to follow the time of the day. The study indicated local as well as systemic effects from previous biopsy sampling.
Randomized Controlled Trial of a Computerized Decision Aid on Adjuvant Radioactive Iodine Treatment for Patients With Early-Stage Papillary Thyroid Cancer
Authors: Anna M. Sawka, Sharon Straus, Lorne Rotstein, James D. Brierley, Richard W. Tsang, Sylvia Asa, Phillip Segal, Catherine Kelly, Afshan Zahedi, Jeremy Freeman, Philip Solomon, Jennifer Anderson, Kevin E. Thorpe, Amiram Gafni, Gary Rodin, David P. Goldstein
Journal: Journal of Clinical Oncology (2012)

Decision-making on adjuvant radioactive iodine (RAI) treatment for early-stage papillary thyroid cancer (PTC) is complex because of uncertainties in medical evidence. Using a parallel, two-arm, randomized, controlled trial design, we examined the impact of a patient-directed computerized decision aid (DA) on the medical knowledge and decisional conflict in patients with early-stage PTC considering the choice of being treated with adjuvant RAI or not. The DA describes the rationale, possible risks and benefits, and the medical evidence uncertainty relating to the choice.We recruited 74 patients with early-stage PTC after thyroidectomy. Participants were assigned by using 1:1 central computerized randomization to either the DA group with usual care (intervention) or usual care alone (control). Medical knowledge about PTC and RAI treatment (the primary outcome), as well as decisional conflict (a secondary outcome), were measured by using validated questionnaires, and the respective scores were compared between groups.Consistent with PTC epidemiology, 83.8% (62 of 74) of the participants were women, and the mean age was 45.8 years (range, 19 to 79 years). Medical knowledge about PTC and RAI treatment was significantly greater and decisional conflict was significantly reduced in the DA group compared with the control group (respective P values < .001). The use of adjuvant RAI treatment was not significantly different between groups (DA group, 11 of 37 [29.7%]; controls, seven of 37 [18.9%]; P = .278).A computerized DA improves informed decision making in patients with early-stage PTC who are considering adjuvant RAI treatment. DAs are useful for patients facing decisions subject to medical evidence uncertainty.
Maintenance of Basal Insulin Secretion in Severe Non-Insulin-Dependent Diabetes
Authors: Michael E Kingston, Warren C Skoog
Journal: Diabetes Care (1986)

It has been postulated that glucose regulation is secondary to maintenance of normal basal insulin secretion. Serum glucose, insulin, and C-peptide levels were measured at fasting in 209 consecutive non-insulin-dependent diabetic patients and after glucose stimulation in 193 patients. The basal serum insulin C-peptide levels were not significantly different in control subjects (mean 22 ± 8.8 μU/ml) and in patients with varying severity of diabetes (mean 24 ± 9.6 μU/ml) except in the most severely diabetic group [fasting serum glucose &amp;gt;350 mg/dl (19.4 mmol/L), mean 19± 7 μU/ml]. In 39 patients who developed ketonuria without acidosis during follow-up, the mean basal serum insulin was 22 μU/ml during the episode of ketonuria, 21 μU/ml during the glucose tolerance test, and 25 μU/ml after glucose stimulation (statistically nonsignificant differences). Our data suggest that hyperglycemia compensates for β-cell impairment so that basal insulin secretion usually stays above the threshold for ketoacidosis unless there is marked β-cell impairment. Patients who fail to increase insulin in response to nutrient challenge are at risk of developing ketosis.
Effects of Parathyroid Hormone on Skeletal Muscle Protein and Amino Acid Metabolism in the Rat
Authors: Alan J. Garber
Journal: Journal of Clinical Investigation (1983)

Because prominent skeletal muscle dysfunction and muscle wasting are seen in both chronic uremia and in primary hyperparathyroidism, and because markedly elevated parathyroid hormone levels occur in both disorders, potential effects of parathyroid hormone on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism were studied in vitro using isolated intact rat epitrochlearis skeletal muscle preparations. Intact bovine parathyroid hormone and the synthetic 1-34 fragment of this hormone stimulated the release of alanine and glutamine from muscle of control but not from chronically uremic animals. This stimulation was dependent upon the concentration of parathyroid hormone added: At 105 ng/ml parathyroid hormone increased alanine release 84% and glutamine release 75%. Intracellular levels of alanine and glutamine were not altered by parathyroid hormone. Increasing concentrations of the 1-34 polypeptide decreased [3H]leucine incorporation into protein of muscles from both control and uremic animals. Using muscles from animals given a pulse-chase label of [guanido-14C]arginine in vivo, parathyroid hormone increased the rate of loss of 14C label from acid-precipitable protein during incubation and correspondingly increased the rate of appearance of this label in the incubation media. Parathyroid hormone increased muscle cAMP levels by 140% and cGMP levels by 185%, but had no effect on skeletal muscle cyclic nucleotide phosphodiesterase activities as assayed in vitro. Adenylyl cyclase activity in membrane preparations from control but not uremic rats was stimulated by parathyroid hormone in a concentration-dependent fashion. However, no stimulation of guanylyl cyclase activity was noted by parathyroid hormone, although stimulation by sodium azide was present. Incubation of muscles with added parathyroid hormone produced a diminished responsiveness towards epinephrine or serotonin regulation of amino acid release and cAMP formation in the presence compared to the absence of parathyroid hormone. In the absence of parathyroid hormone, detectable inhibition of alanine and glutamine release was produced by 10−9 M epinephrine, whereas in the presence of parathyroid hormone (1,000 ng/ml) inhibition of alanine and glutamine release required 10−6 M or greater epinephrine. Resistance to cyclic AMP action as well as inhibition of cyclic AMP formation by parathyroid hormone was found. Preincubation of rat sarcolemma with 1-34 parathyroid hormone produced a decreased activity of the isoproterenol-stimulable adenylyl cyclase activity but there was no apparent change in the concentration of isoproterenol required for one-half maximal and maximal stimulation of the enzyme.