tbuckley/cabot-search huggingface dataset:
Crypt stem cell survival in the mouse intestinal epithelium is regulated by prostaglandins synthesized through cyclooxygenase-1.
Authors: S M Cohn, S Schloemann, T Tessner, K Seibert, W F Stenson
Journal: Journal of Clinical Investigation (1997)

Prostaglandins (PGs) are important mediators of epithelial integrity and function in the gastrointestinal tract. Relatively little is known, however, about the mechanism by which PGs affect stem cells in the intestine during normal epithelial turnover, or during wound repair. PGs are synthesized from arachidonate by either of two cyclooxygenases, cyclooxygenase-1 (Cox-1) or cyclooxygenase-2 (Cox-2), which are present in a wide variety of mamalian cells. Cox-1 is thought to be a constitutively expressed enzyme, and the expression of Cox-2 is inducible by cytokines or other stimuli in a variety of cell types. We investigated the role of PGs in mouse intestinal stem cell survival and proliferation following radiation injury. The number of surviving crypt stem cells was determined 3.5 d after irradiation by the microcolony assay. Radiation injury induced a dose-dependent decrease in the number of surviving crypts. Indomethacin, an inhibitor of Cox-1 and Cox-2, further reduced the number of surviving crypts in irradiated mice. The indomethacin dose response for inhibition of PGE2 production and reduction of crypt survival were similar. DimethylPGE2 reversed the indomethacin-induced decrease in crypt survival. Selective Cox-2 inhibitors had no effect on crypt survival. PGE2, Cox-1 mRNA, and Cox-1 protein levels all increase in the 3 d after irradiation. Immunohistochemistry for Cox-1 demonstrated localization in epithelial cells of the crypt in the unirradiated mouse, and in the regenerating crypt epithelium in the irradiated mouse. We conclude that radiation injury results in increased Cox-1 levels in crypt stem cells and their progeny, and that PGE2 produced through Cox-1 promotes crypt stem cell survival and proliferation.
Effect of calcitonin gene-related peptide on coronary microvessels and its role in acute myocardial ischemia.
Authors: N Sekiguchi, H Kanatsuka, K Sato, Y Wang, K Akai, T Komaru, T Takishima
Journal: Circulation (1994)

Calcitonin gene-related peptide (CGRP) is a potent dilator of epicardial conduit vessels and is released during myocardial ischemia in humans. However, the effect of CGRP on coronary arterial microvessels is still unclear, and it is unknown if CGRP modulates the tone of coronary arterial microvessels during acute myocardial ischemia.Epimyocardial microvessels were observed through a microscope equipped with a floating objective system in anesthetized open-chest dogs. Heart rate and aortic pressure were maintained at control levels. Flow velocity of the left anterior descending coronary artery (LAD) was measured with a suction-cup Doppler probe. When CGRP was cumulatively infused into the LAD (0.05, 0.5, 5.0, and 50 pmol/kg per minute) or superfused (0.03, 0.3, 3.0, and 30 nmol/L) over the left ventricular surface, arterial control microvessels > 100 microns in diameter dilated dose dependently at dosages of 0.5 to 50 pmol/kg per minute (infused) or 0.3 to 30 nmol/L (superfused), but those < 100 microns dilated only at the highest dose, and those > 100 microns had greater dilation in both groups. Only the highest dose of CGRP (infused) significantly increased coronary flow. The superfusion of CGRP(8-37) (CGRP receptor antagonist, 300 nmol/L) did not affect the control diameters of coronary arterial microvessels but completely abolished CGRP-induced vasodilation at the same doses (infused and superfused). However, 300 nmol/L of CGRP(8-37) did not affect the response of coronary arterial microvessels to the LAD occlusion in any size.CGRP preferentially dilates the coronary arterial microvessels > 100 microns in diameter but has only a small effect on those < 100 microns. Endogenous CGRP does not modulate the tone of coronary arterial microvessels during acute myocardial ischemia in beating canine hearts.
Loss of Heterozygosity at the Thymidylate Synthase (<b> <i>TS</i> </b>) Locus on Chromosome 18 Affects Tumor Response and Survival in Individuals Heterozygous for a 28-bp Polymorphism in the <b> <i>TS</i> </b> Gene
Authors: Kazumi Uchida, Kazuhiko Hayashi, Kazuyuki Kawakami, Sylke Schneider, Ji Min Yochim, Hidekazu Kuramochi, Ken Takasaki, Kathleen D. Danenberg, Peter V. Danenberg
Journal: Clinical Cancer Research (2004)

Thymidylate synthase (TS), the target enzyme of the fluoropyrimidine class of drugs, has a 28-bp repeat polymorphism in the promoter region that has been associated with response of tumors to 5-fluorouracil-based therapy. Patients homozygous for the double repeat (2R/2R) in the TS gene have an overall better outcome from treatment than patients homozygous for the triple repeat (3R/3R). However, due to loss of heterozygosity at the TS locus on chromosome 18 in cancer cells, heterozygous 2R/3R individuals can acquire the 2R/loss or the 3R/loss genotype in their tumors. The purpose of this study was to determine whether the response of colorectal cancer to fluoropyrimidine therapy is associated with the resulting tumor TS genotype when loss of heterozygosity occurs in tumor DNA. A total of 30 colorectal cancer patients treated with the fluoropyrimidine-based combination S-1, all of whom had stage IV disease, were studied. The response rate to S-1 in this group of patients was 13 of 30 (43%). The heterozygous 2R/3R genotype was found in 22 of 30 normal tissues, whereas 10 (45%) of the matched cancer tissues showed only the 2R-sequence band (2R/loss), and 7 cancer tissues (32%) showed only the 3R-sequence band (3R/loss). The response rate of the 2R/loss tumor genotype patients was 80% (8 of 10) compared with 14% (1 of 7) in the 3R/loss genotype group (P = 0.029). Patients with tumor 3R/loss genotypes had significantly lower survival than 2R/loss genotypes. Heterozygous patients with a 2R/loss tumor genotype had the same survival as 2R/2R patients, whereas patients with a 2R/3R tumor genotype had a short survival similar to homozygous 3R/3R genotypes. These results show that: (a) response to 5-fluorouracil-based therapy is determined by tumor genotype; and (b) the 3R repeat is a direct negative determinant of outcome.
Pancreatic GLP-1 receptor activation is sufficient for incretin control of glucose metabolism in mice
Authors: Benjamin J. Lamont, Yazhou Li, Edwin Kwan, Theodore J. Brown, Herbert Gaisano, Daniel J. Drucker
Journal: Journal of Clinical Investigation (2011)

Glucagon-like peptide-1 (GLP-1) circulates at low levels and acts as an incretin hormone, potentiating glucose-dependent insulin secretion from islet β cells. GLP-1 also modulates gastric emptying and engages neural circuits in the portal region and CNS that contribute to GLP-1 receptor-dependent (GLP-1R-dependent) regulation of glucose homeostasis. To elucidate the importance of pancreatic GLP-1R signaling for glucose homeostasis, we generated transgenic mice that expressed the human GLP-1R in islets and pancreatic ductal cells (Pdx1-hGLP1R:Glp1r-/- mice). Transgene expression restored GLP-1R-dependent stimulation of cAMP and Akt phosphorylation in isolated islets, conferred GLP-1R-dependent stimulation of β cell proliferation, and was sufficient for restoration of GLP-1-stimulated insulin secretion in perifused islets. Systemic GLP-1R activation with the GLP-1R agonist exendin-4 had no effect on food intake, hindbrain c-fos expression, or gastric emptying but improved glucose tolerance and stimulated insulin secretion in Pdx1-hGLP1R:Glp1r-/- mice. i.c.v. GLP-1R blockade with the antagonist exendin(9-39) impaired glucose tolerance in WT mice but had no effect in Pdx1-hGLP1R:Glp1r-/- mice. Nevertheless, transgenic expression of the pancreatic GLP-1R was sufficient to normalize both oral and i.p. glucose tolerance in Glp1r-/- mice. These findings illustrate that low levels of endogenous GLP-1 secreted from gut endocrine cells are capable of augmenting glucoregulatory activity via pancreatic GLP-1Rs independent of communication with neural pathways.
The Crisis in Local Institutional Review Boards
Authors: Alan M. Sugar
Journal: Annals of Internal Medicine (2002)

Letters5 March 2002The Crisis in Local Institutional Review BoardsAlan M. Sugar, MDAlan M. Sugar, MDBoston University School of Medicine; Wellesley, MA 02481 (Sugar)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-136-5-200203050-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The papers by Burman and colleagues (1) and Levine (2) highlight problems in clinical research. However, there are additional factors. None of the suggestions in these papers seem to enhance the IRB's protection of research subjects.The IRB workload has increased enormously (3), but this is not due solely to the increase in the number of multicenter clinical studies. Investigator-initiated trials and study complexity have increased, resulting in the need for expertise in evaluating the studies and methods for suitably explaining protocols to prospective subjects.One major problem is emphasis on regulation and paperwork, often at the ...References1. Burman WJ, Reves RR, Cohn DL, Schooley RT. Breaking the camel's back: multicenter clinical trials and local institutional review boards. Ann Intern Med. 2001;134:152-7. [PMID: 11177319] LinkGoogle Scholar2. Levine RJ. Institutional review boards: a crisis in confidence [Editorial]. Ann Intern Med. 2001;134:161-3. [PMID: 11177321] LinkGoogle Scholar3. . Protecting Human Research Subjects: Status of Recommendations. Department of Health and Human Services, Office of the Inspector General. Washington, DC: U.S. Department of Health and Human Services; 2000. Google Scholar4. Hammerschmidt DE, Keane MA. Institutional Review Board (IRB) review lacks impact on the readability of consent forms for research. Am J Med Sci. 1992;304:348-51. [PMID: 1456273] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Boston University School of Medicine; Wellesley, MA 02481 (Sugar) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoInstitutional Review Boards: A Crisis in Confidence Robert J. Levine Breaking the Camel's Back: Multicenter Clinical Trials and Local Institutional Review Boards William J. Burman , Randall R. Reves , David L. Cohn , and Robert T. Schooley The Crisis in Local Institutional Review Boards Stephanie Nagy-Agren The Crisis in Local Institutional Review Boards William J. Burman and Randall R. Reves The Crisis in Local Institutional Review Boards Jamie Ellen Siegel , Ann Vaughn , and Elaine Baszczewski Metrics 5 March 2002Volume 136, Issue 5Page: 410KeywordsEmotionsInstitutional review boards ePublished: 5 March 2002 Issue Published: 5 March 2002 CopyrightCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Design and evaluation of genome-wide libraries for RNA interference screens
Authors: Thomas Horn, Thomas Sandmann, Michael Boutros
Journal: Genome biology (2010)

Abstract RNA interference (RNAi) screens have enabled the systematic analysis of many biological processes in cultured cells and whole organisms. The success of such screens and the interpretation of the data depend on the stringent design of RNAi libraries. We describe and validate NEXT-RNAi, a software for the automated design and evaluation of RNAi sequences on a genome-wide scale. NEXT-RNAi is implemented as open-source software and is accessible at http://www.nextrnai.org/.
Etiology of nephrocalcinosis in preterm neonates: Association of nutritional intake and urinary parameters
Authors: Eveline A. Schell-Feith, Joana E. Kist-van Holthe, Nikk Conneman, Paul H.T. van Zwieten, Herma C. Holscher, Harmine M. Zonderland, Ronald Brand, Bert J. van der Heijden
Journal: Kidney International (2000)
Degree of CD25 Expression in T-Cell Lymphoma Is Dependent on Tissue Site
Authors: Dan Jones, Sherif Ibrahim, Kaushali Patel, Rajyalakshmi Luthra, Madeleine Duvic, L. Jeffrey Medeiros
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Using concurrent tumor samples from different anatomical sites, we compared expression of the therapeutic targets CD25 and CD30 in T-cell lymphoma (TCL). Experimental Design: We examined levels of CD25 and CD30 by flow cytometry in tumor cells from peripheral blood and lymph node in 13 cutaneous TCL patients and by immunohistochemistry in concurrent lymph node and skin biopsy specimens in 17 additional TCL cases, mostly mycosis fungoides. Tumor cell expression was correlated with patterns of expression in nonneoplastic lymphocytes in 14 reactive lymph node and 10 skin samples showing chronic dermatitis. Expression of CD25 and CD30 in all biopsy samples was compared with that of cutaneous lymphocyte antigen (CLA), a mediator of skin homing. Results: By flow cytometry, we noted significantly decreased expression of CD25 in lymph node compared with peripheral blood in 8 of 13 TCLs, with no changes in CD30 levels in 4 cases studied. Using immunohistochemistry, CD25 was strongly expressed in epidermotropic tumor cells in 13 of 17 (76%) TCL skin specimens but was decreased in the corresponding lymph node in 12 of these cases. CD30 was expressed at roughly equal intensity in tumor cells from both sites, except in 1 case. CLA showed a similar pattern to CD25, being expressed by tumor cells in 16 of 17 (94%) skin specimens, but was largely absent in tumor cells in the corresponding lymph node in 12 of these patients. In T cells from reactive lymph node biopsy specimens, CD25 was highly expressed only in dermatopathic lymphadenitis associated with transient skin rashes. Conclusions: We demonstrate in vivo that decreased levels of CD25 expression occur in TCL when it involves lymph node, similar to what is seen with CLA. This demonstrable variation related to anatomical localization has implications for the measurement of surface expression of CD25 and for understanding the response of patients with cutaneous TCL to interleukin 2 receptor-targeted immunotherapy.
Vertebral Wedge Osteotomy
Authors: Vincent A. Scudese
Journal: JAMA (1963)

Rheumatoid (ankylosing) spondylitis occurs infrequently in women, in whom it appears to run a milder course. Though a rigid lumbar kyphosis is a common sequela of ankylosing spondylitis, only a small number of patients require osteotomy of the spine. The case is presented of a young woman on whom wedge osteotomy was performed successfully. A method of posterior vertebral body wedge resection for correction of lumbar kyphosis in patients with ankylosing spondylitis is described. The method consists of resection of a portion of the posterior neural elements, lumbar disc, and vertebral body with subsequent manipulation of the spine into extension. The principle of the modified surgical method prevents lengthening of the lumbar spine, thus eliminating stretching and injury to juxtaposed organs.
A patient with paroxysmal nocturnal hemoglobinuria, T cell large granular lymphocyte clonal expansion, and monoclonal gammopathy of undetermined significance
Authors: Jon S. Fukumoto, Jason Gotlib
Journal: American Journal of Hematology (2006)

Paroxysmal nocturnal hemoglobinuria (PNH) has been described in association separately with T cell large granular lymphocyte (LGL) clonal expansions and plasma cell dyscrasias. We describe a patient with anemia related to hemolytic PNH, with concurrent T cell LGL oligoclonal expansion and IgG λ monoclonal gammopathy of undetermined significance. Peripheral blood flow cytometry revealed decreased expression of CD55 and CD59 on erythrocytes and decreased expression of CD55 and CD66 on neutrophils. An LGL population was present in the peripheral blood and was characterized as oligoclonal by polymerase chain reaction-based analysis of the T cell receptor γ-chain variable region. Serum protein electrophoresis with immunofixation showed a low level IgG λ monoclonal protein. We describe the diagnostic evaluation of this patient and provide a brief review of the reported associations among PNH, LGL clonal expansion, and monoclonal gammopathy. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc.
Intravascular and Extravascular Hemolysis Accompanying Extracorporeal Circulation
Authors: HERBERT W. WALLACE, WILLIAM S. BLAKEMORE
Journal: Circulation (1970)

Eleven patients undergoing open heart surgery were studied by means of a technic previously developed by us to quantitate intravascular and extravascular hemolysis. Endogenous production of carbon monoxide, which correlates quantitatively with red blood cell and hemoglobin catabolism, was measured preoperatively, 5 hr postoperatively, and 24 hr postoperatively. Rates of plasma hemoglobin catabolism and intravascular hemolysis were calculated from serial plasma hemoglobin determinations. Extravascular hemolysis results from catabolism of erythrocytes damaged during perfusion and subsequently sequestered in the reticuloendothelial system. Intravascular hemolysis occurred only during perfusion and averaged 252.22 ± se 49.64 µmoles heme. Extravascular hemolysis measured for the first 5 hr after perfusion averaged 462.48 ± se 68.70 µmoles heme, or 64% of the total calculated red blood cell destruction. In all but one of the eight patients studied 24 hr after perfusion, heme catabolism remained elevated (mean, 46.76 ± se 13.05 µmoles heme/hr compared to a normal value of ≦22 µmoles heme/hr), indicating that extravascular hemolysis was still occurring. This extravascular destruction probably resulted from alterations in the cell membrane induced during the pumping procedure.
High frequency of BRAF mutations in nevi
Authors: Pamela M. Pollock, Ursula L. Harper, Katherine S. Hansen, Laura M. Yudt, Mitchell Stark, Christiane M. Robbins, Tracy Y. Moses, Galen Hostetter, Urs Wagner, John Kakareka, Ghadi Salem, Tom Pohida, Peter Heenan, Paul Duray, Olli Kallioniemi, Nicholas K. Hayward, Jeffrey M. Trent, Paul S. Meltzer
Journal: Nature Genetics (2002)
Semiquantitative Analysis of the Histopathological Features of the Neuropathic Foot Ulcer
Authors: Alberto Piaggesi, Paolo Viacava, Loredana Rizzo, Giuseppe Naccarato, Fabio Baccetti, Marco Romanelli, Virna Zampa, Stefano Del Prato
Journal: Diabetes Care (2003)

OBJECTIVE—This study was designed to evaluate the histopathology of neuropathic ulcers and whether pressure relief could change such histological patterns. RESEARCH DESIGN AND METHODS—We compared neuropathic plantar ulcers tissue excised from 10 diabetic patients (group A) with those taken from 10 patients with comparable lesions and glycemic control after 20 days in a total contact cast (group B). Tissue specimens were blindly examined by two independent pathologists for hyperkeratosis, fibrosis, cutaneous annexes, capillaries, inflammation, cellular debris, and granulating tissue. For each parameter, quantification was obtained according to an arbitrary score: 0, absent; 1, present in &amp;lt;33%; 2, present in 34–66%; and 3, present in &amp;gt;67% of the lesion. RESULTS—Patients in group B showed a marked reduction in ulcer size after 20 days of casting (P &amp;lt; 0.01). The histopathological features of the two groups markedly differed. Group A patients showed a predominance of inflammatory elements as well as matrix alterations, vessel disruptions, inflammation, and debris. Group B ulcers showed a shift toward a reparative pattern with prevalence of neoformed capillaries and fibroblasts. Semiquantitative analysis confirmed the prevalence of hyperkeratosis, fibrosis, inflammation, and cellular debris in group A patients (P &amp;lt; 0.05), whereas cutaneous annexes, capillaries, and granulating tissue were more prevalent in group B lesions (P &amp;lt; 0.01). CONCLUSIONS—These results indicate that pressure relief with a total contact cast is associated with changes in the histology of neuropathic foot ulcers, indicating reduction of inflammatory and reactive components and acceleration of reparative processes.
NOTES ON A CASE OF NAEVO-CARCINOMA (MELANOTIC) OF THE SCALP IN A BOY AGED NINETEEN YEARS
Authors: CHARLES H. LILLEY
Journal: British Journal of Dermatology (1912)

Journal Article NOTES ON A CASE OF NÆVO‐CARCINOMA (MELANOTIC) OF THE SCALP IN A BOY AGED NINETEEN YEARS Get access CHARLES H. LILLEY, M.B., Ch.B.St. And. CHARLES H. LILLEY, M.B., Ch.B.St. And. Late Senior House‐Surgeon, Royal Hospital, Exeter Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 24, Issue 12, 1 December 1912, Pages 411–413, https://doi.org/10.1111/j.1365-2133.1912.tb16709.x Published: 01 December 1912
RELATIONSHIP OF DONOR AGE TO IN VITRO PRODUCTION OF FOOT-AND-MOUTH DISEASE VIRUS BY MOUSE KIDNEY CELLS
Authors: Charles H. Campbell
Journal: The Journal of Experimental Medicine (1965)

Multiplication of foot-and-mouth disease virus (FMDV) was compared in kidney cells from 7- to 35-day-old mice representing various degrees of age resistance to this virus. Three types of cell preparations were used: primary monolayer cultures, suspensions of dispersed cells, and suspensions of minced tissue. Virus multiplication in the two types of cell suspensions was related to the age of the donors both in regard to time when multiplication first became evident and to the amount of virus produced. While adsorption rates were similar in the cells from all age groups, virus multiplication began earlier in cells from younger mice and more virus was produced by these cells than by cells from older animals. There was no significant difference in the virus growth rates in the primary monolayer cultures of cells. The results indicate that kidney cells from mice 7 to 35 days old vary in their ability to produce virus in relation to the degree of susceptibility of the cell donors. After propagation of the cells in primary monolayer cultures, however, this difference no longer exists probably because of cell selection under the cultural conditions.
Treatment of chronic hepatitis C in hemodialysis patients
Authors: Marina Berenguer
Journal: Hepatology (2008)

Abstract Hepatitis C virus (HCV) infection is especially problematic in patients with end-stage renal disease (ESRD) who are undergoing hemodialysis. Rates of HCV infection are higher among hemodialysis patients than in the general population, and several routes of transmission are thought to stem from the dialysis unit. Management of chronic hepatitis C is also more complicated in hemodialysis patients because of altered pharmacokinetics and a predisposition for drug-related toxicity, particularly ribavirin-induced anemia. Clinical trials of patients with chronic hepatitis C and healthy, functioning kidney grafts are rare because of the inherent dangers of graft rejection. As a result, most studies in patients with ESRD have focused on patients waiting for a kidney transplant. Additionally, because ribavirin is contraindicated in this patient population, many studies have examined monotherapy treatments. According to meta-analyses, conventional interferon alfa treatment yields a sustained virological response (SVR) rate of 37%, whereas studies of pegylated interferon alfa monotherapy have yielded SVR rates between 13% and 75%. Several small studies have also used the monitoring of ribavirin plasma concentrations or hemoglobin levels to facilitate the use of combination therapy. In light of the results from these clinical trials, we herein review treatment guidelines and recommend strategies to help optimize the treatment of patients with ESRD. Conclusion: There remains a lack of clarity surrounding the most effective treatment options for patients with chronic hepatitis C and ESRD. Treatment can be effective with many patients attaining SVR; however, unfavorable tolerability with interferon alfa–based therapy remains a concern and thus close supportive care should be aggressively pursued to help maintain adherence. (Hepatology 2008;48:1690–1699.)