Search

Your search keyword '"R. Hansen"' showing total 36 results
Start Over Author "R. Hansen" Publisher oxford university press
36 results on '"R. Hansen"'

1. PSXVI-12 Revolutionizing in vitro endometrial cell studies: A novel methodology to obtain bovine endometrial cells

Author

John P. Driver, Felipe Alves Correa Carvalho da Silva, Mario Binelli, T. Martins, Marcela G. Marrero, Thomas R. Hansen, John J. Bromfield, and Cecilia Constantino Rocha

Subjects
Poster Presentations, Chemistry, Genetics, Cancer research, Animal Science and Zoology, General Medicine, In vitro, Food Science, Endometrial cell
Abstract

Cultured primary endometrial cells are used extensively to study uterine function in cattle. However, most protocols harvest endometrial cells from slaughtered animals at estimated stages of the estrous cycle. The goal of this study was to establish and validate an in vivo, minimally invasive, and estrous cycle stage-specific method to obtain endometrial cells for culture. In Experiment 1, the uterine body of Bos indicus-influenced cows was sampled using a cytology brush (cytobrush) 4 days post estrus (D4; n = 13). Brushes were transported in medium (DMEM/F12, 3% Penicillin/Streptomycin and 2% of Fungizone) to the laboratory at ambient temperature. Cells were cultured in medium containing 10% FBS at 5% of CO2 (38°C). Confluent cells (~7 days of culture) were sub-cultured for two subsequent passages. Pools (n = 4) of cells from 2–3 animals, were frozen, thawed, and re-plated (passage 3). The relative transcript abundance of PPIA, ACTB, KRT18, VIM, OXTR, PGR, ESR1 and IFNAR1 were analyzed by qPCR and compared among fresh cells and cells from each passage. Abundance of KRT18 and VIM transcripts was similar across passages, while PGR, ESR1, OXTR and IFNAR1 transcripts decreased by 90, 96, 84, and 82 %; respectively in cultured compared to fresh cells (P < 0.05). In Experiment 2, passage 3 cells were cultured for 24 hours with 0 or 1ng/mL of recombinant bovine interferon-tau (rbIFNT; n = 3 replicates/treatment). The relative expression of a classical interferon stimulated gene, ISG15, was evaluated by qPCR. Expression of ISG15 was 6-fold greater (P < 0.05) in the rbIFNT treated cells compared to controls. In conclusion, the culture of endometrial cells collected by cytobrush is feasible, generates a monolayer enriched in epithelial cells and may be used as a model for physiological studies involving IFNT signaling. Further experiments to ascertain the physiological relevance of this model are underway.

Published
2021

2. 135 Effect of Gossypol from Cottonseed Meal on Growth Performance, Plasma Gossypol, and Complete Blood Cell Counts in Commercial Growing Pigs: A Preliminary Study on Feral Hog Control

Author

Brittni P Littlejohn, Rick Rorie, Richard A Mudarra, Christopher R Hansen, Charles V Maxwell, and Tsung Cheng Cheng Tsai

Subjects
General Medicine, Biology, Blood cell, chemistry.chemical_compound, Animal science, medicine.anatomical_structure, chemistry, Gossypol, Genetics, medicine, Oral Presentations, Animal Science and Zoology, Cottonseed meal, Food Science
Abstract

To evaluate the effect of cottonseed meal (CSM) on growth performance, plasma gossypol and complete blood cell (CBC) counts in growing pigs, 40 gilts (Exp 1) and 24 boars (Exp 2), 63 day of age (19.85±0.43 kg), were randomly allotted to 1 of 4 and 3 treatments with 2 replicates/treatments, respectively. Treatments for Exp 1 during phase 1–3 (14 d/phase) were a nutrient adequate control diet (NRC, 2012) without CSM (0% gossypol), and increasing levels of CSM was added to produce diets containing 0.01%, 0.02% and 0.04% gossypol to form treatments 2 to 4, respectively. For Exp 2, treatments were the same as those in the gilt trail, except 0.01% gossypol treatment was eliminated. All pigs were fed a common diet without CSM in phase 4 (14 d). Whole blood was obtained from two close-to-average pen-BW pigs repeatedly at each phase to determine CBC in Exp 1 and plasma gossypol in Exp 1 and 2. Data were analyzed using the Mixed procedures of SAS (Cary, NC). ADG did not significantly differ between treatments in phase 1&2 (P > 0.05). In phase 3, ADG decreased linearly and quadratic (P < 0.05) with increasing level of CSM in gilts and boars, respectively, while ADFI did not differ. Neutrophil concentration was higher while mean corpuscular volume (MCV) was lower in gilts fed CSM on d 42 than those fed control regardless level of inclusion, whereas after 14 d of CSM withdrawal, neutrophil level was similar to control and MCV remained low (Treatment*day, P < 0.01). Plasma gossypol increased with increasing level of CSM in both gilts and boars during phase 1–3, and was still higher than control after pigs were fed a common diet for 14 d (P < 0.05). In conclusion, cottonseed meal derived gossypol impairs growth performance, and increase plasma gossypol in gilts and boars.

Published
2021

3. Applications of Circulating Tumor DNA in a Cohort of Phase I Solid Tumor Patients Treated With Immunotherapy

Author

Dax Torti, Eric Plackmann, Aoife J McCarthy, Helen Chow, Aaron R. Hansen, Alberto Leon, Kayla Marsh, Lisa Wang, Daniel Vilarim Araujo, Hal K. Berman, Anna Spreafico, Xue Wu, Lillian L. Siu, Hua Bao, Philippe L. Bedard, Albiruni-Abdul Razak, Trevor J. Pugh, and Ao Wang

Subjects
Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, DNA Mutational Analysis, Phases of clinical research, Pilot Projects, Kaplan-Meier Estimate, medicine.disease_cause, Article, Circulating Tumor DNA, Cohort Studies, 03 medical and health sciences, Mutation Accumulation, Young Adult, 0302 clinical medicine, Internal medicine, Neoplasms, medicine, Humans, Solid tumor, Allele frequency, Immune Checkpoint Inhibitors, 030304 developmental biology, Aged, Proportional Hazards Models, 0303 health sciences, Mutation, Paraffin Embedding, Clinical Trials, Phase I as Topic, business.industry, Immunotherapy, Exploratory analysis, Middle Aged, Prognosis, Treatment Outcome, Circulating tumor DNA, 030220 oncology & carcinogenesis, Cohort, Female, business, AcademicSubjects/MED00010
Abstract

Background The correlation between blood-based tumor mutation burden (bTMB) and tissue-based tumor mutation burden(tTMB) has not been broadly tested in a multicancer cohort. Here, we assess the correlation between bTMB with tTMB in phase I trial patients treated with immunotherapy. As an exploratory analysis, we evaluated circulating tumor DNA (ctDNA) dynamics in responders. Methods Patients treated with immunotherapy at the Princess Margaret phase I trials unit were enrolled. Pretreatment plasma ctDNA and matched normal blood controls were collected. Available archival tissue formalin-fixed paraffin-embedded (FFPE) samples were analyzed. A 425-gene panel was used to sequence both ctDNA and FFPE samples. Samples with TMB within the highest tertile were considered as high TMB. Results Thirty-eight patients were accrued from 25 different trials, 86.8% of which involved an anti-PD-1/PD-L1 agent. Thirty patients (78.9%) had detectable mutations in ctDNA, of which the median (range) bTMB was 5 (1-53) mutations per megabase (mut/Mb). Of the 22 patients with available FFPE samples, mutations were detected in 21 (95.4%); the median (range) tTMB was 6 (2-124) mut/Mb. Among the 16 patients with detectable mutations in both FFPE and ctDNA, a statistically significant correlation between bTMB and tTMB was observed (ρ = 0.71; P = .002). High TMB was not associated with better survival. All 3 responders had a decrease in the variant allele frequency of mutations detected in ctDNA at a second timepoint relative to baseline, indicating a potential early marker of response. Conclusions In this small series, bTMB correlated with tTMB. An on-treatment decrease in VAF of mutations detected in ctDNA at baseline was observed in responders. Larger studies to verify our findings are warranted.

Published
2021

4. Systematic Review and STARD Scoring of Renal Cell Carcinoma Circulating Diagnostic Biomarker Manuscripts

Author

Marco A. J. Iafolla, Sarah Picardo, Kyaw L. Aung, and Aaron R. Hansen

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Receiver operating characteristic, business.industry, MEDLINE, Kidney Carcinoma, Cancer, Review, medicine.disease, Cell-free fetal DNA, Renal cell carcinoma, Internal medicine, medicine, Medical diagnosis, business, AcademicSubjects/MED00010, Kidney cancer
Abstract

Background No validated molecular biomarkers exist to help guide diagnosis of renal cell carcinoma (RCC) patients. We seek to evaluate the quality of published RCC circulating diagnostic biomarker manuscripts using the Standards for Reporting of Diagnostic Accuracy Studies (STARD) guidelines. Methods The phrase “(renal cell carcinoma OR renal cancer OR kidney cancer OR kidney carcinoma) AND circulating AND (biomarkers OR cell free DNA OR tumor DNA OR methylated cell free DNA OR methylated tumor DNA)” was searched in Embase, MEDLINE, and PubMed in March 2018. Relevant manuscripts were scored using 41 STARD subcriteria for a maximal score of 26 points. All tests of statistical significance were 2 sided. Results The search identified 535 publications: 27 manuscripts of primary research were analyzed. The median STARD score was 11.5 (range = 7-16.75). All manuscripts had appropriate abstracts, introductions, and distribution of alternative diagnoses. None of the manuscripts stated how indeterminant data were handled or if adverse events occurred from performing the index test or reference standard. Statistically significantly higher STARD scores were present in manuscripts reporting receiver operator characteristic curves (P < .001), larger sample sizes (P = .007), and after release of the original STARD statement (P = .005). Conclusions Most RCC circulating diagnostic biomarker manuscripts poorly adhere to the STARD guidelines. Future studies adhering to STARD guidelines may address this unmet need.

Published
2020

5. Families with children resulting from ART: psychosocial and financial implications

Author

Michael P. Diamond, Virginia M. Miller, Hao Huang, Christos Coutifaris, Marcelle I. Cedars, Heping Zhang, Karl R. Hansen, Nanette Santoro, Stephen A. Krawetz, Richard S. Legro, and Anne Z. Steiner

Subjects
Finance, medicine.medical_specialty, education.field_of_study, Assisted reproductive technology, business.industry, medicine.medical_treatment, media_common.quotation_subject, Population, Reproductive medicine, Beck Depression Inventory, Fertility, Confidence interval, Checklist, psychosocial implications of ART, assisted reproductive technology, medicine, Original Article, financial implications of ART, business, education, Psychology, Psychosocial, ART, media_common
Abstract

STUDY QUESTION What are the psychosocial and financial issues experienced among families with children 2–12 years of age conceived by ART? SUMMARY ANSWER Our results suggest that families with children, 2–12 years of age, conceived via ART are doing well, although impacts were identified on parents of twins and higher-order multiples. WHAT IS KNOWN ALREADY Multiple births have been associated with higher morbidity and mortality of children, as well as financial costs to families and society. STUDY DESIGN, SIZE, DURATION This study was an assessment of familial response to birth of singletons, twins and higher order multiples at child’s ages of 2–12. PARTICIPANTS/MATERIALS, SETTING, METHODS Semi-structured interviews and surveys were conducted with mothers (n = 348) and fathers (n = 338) of singletons, twins and higher-order multiple gestations who received fertility services. MAIN RESULTS AND THE ROLE OF CHANCE No significant differences were observed between the groups in domains of primary caregiving or parental separation/divorce. Impacts were identified on parent’s ability to maintain employment. The revised 15-item scores of the Impact on Family Scale were significantly lower, reflecting more negative impacts, among families with twins (beta = −2.6, 95% confidence interval (CI), −4.7, −0.5, P = 0.014) and multiples (beta = −7.4, 95% CI, −10.4, −4.5, P LIMITATIONS, REASONS FOR CAUTION The study was limited to families who received fertility treatment and constitutes a population that was well educated and had higher incomes. Additionally, interview data was self-reported. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) U10 HD39005 (to M.P.D.), U10 HD077680 (to K.R.H.), U10 HD077844 (to A.Z.), U10 HD077841 (to M.C.), U10 HD38992 (to R.S.L.), U10 HD27049 (to C.C.), U10 HD055925 (to H.Z.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or NIH. Dr Virginia Miller—no conflicts; Dr Michael P. Diamond—NIH Funding, AbbVie, Bayer and ObsEva Funding; Board of Directors and Stockholder for Advanced Reproductive Care; Dr Karl R. Hansen—Yale University/Reproductive Medicine Network/NICHD, Roche Diagnostics and Ferring International Pharmascience Center US funding; Dr Anne Steiner—NIH Funding; Dr Marcelle I. Cedars—no conflicts; Dr Richard Legro—consultant for Ogeda, Millendo, Kindex and Bayer; Ferring and Astra Zeneca funding; Dr Stephen A. Krawetz—no conflicts; Dr Christos Coutifaris—NIH Funding; Dr Hao Huang—no conflicts; Dr Nanette Santoro—no conflicts; Dr Heping Zhang—NIH Funding. TRIAL REGISTRATION NUMBER N/A

Published
2020

6. Infectious Diseases Physicians: Improving and Protecting the Public’s Health: Why Equitable Compensation Is Critical

Author

Matthew Zahn, Noreen A. Hynes, Gail R. Hansen, Rodger D. MacArthur, Amesh A. Adalja, Amanda Jezek, Paul J. Edelson, Paul G. Auwaerter, Colin McGoodwin, Yukari C. Manabe, and Jeffrey S. Duchin

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Population, Subspecialty, Communicable Diseases, compensation, 03 medical and health sciences, 0302 clinical medicine, Physicians, Hospital-acquired infection, medicine, Antimicrobial stewardship, Humans, 030212 general & internal medicine, education, ID physician workforce, Disease surveillance, education.field_of_study, Infection Control, business.industry, Salaries and Fringe Benefits, Public health, Compensation (psychology), public health, Disease Management, medicine.disease, Viewpoints, Infectious Diseases, Family medicine, Workforce, business, value of ID physicians, Specialization
Abstract

Infectious diseases (ID) physicians play a crucial role in public health in a variety of settings. Unfortunately, much of this work is undercompensated despite the proven efficacy of public health interventions such as hospital acquired infection prevention, antimicrobial stewardship, disease surveillance, and outbreak response. The lack of compensation makes it difficult to attract the best and the brightest to the field of ID, threatening the future of the ID workforce. Here, we examine compensation data for ID physicians compared to their value in population and public health settings and suggest policy recommendations to address the pay disparities that exist between cognitive and procedural specialties that prevent more medical students and residents from entering the field. All ID physicians should take an active role in promoting the value of the subspecialty to policymakers and influencers as well as trainees., Infectious diseases (ID) physicians perform valuable roles protecting public health, but many of their activities are poorly compensated. Compensation policy changes are needed to allow the ID field to continue to attract the best and brightest medical students and residents.

Published
2018

7. NIMG-76. POST-GADOLINIUM 3-DIMENSIONAL SPATIAL, SURFACE, AND STRUCTURAL CHARACTERISTICS OF GLIOBLASTOMAS DIFFERENTIATE PSEUDOPROGRESSION FROM TRUE TUMOR PROGRESSION

Author

Andrew D. Wilson, Marco C. Pinho, Darin T. Okuda, Thomas Stanley, Morgan McCreary, Xiaohu Guo, Madison R. Hansen, Yeqi Wang, and Edward Pan

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Abstracts, Oncology, chemistry, Tumor progression, Gadolinium, medicine, chemistry.chemical_element, Neurology (clinical), Pseudoprogression
Abstract

PURPOSE: Pseudoprogression is often indistinguishable from true tumor progression on conventional 2-dimensional (2D) MRI in glioblastoma multiforme (GBM) patients. The aim of this study was to determine the association between post-gadolinium 3-dimensional (3D) characteristics and clinical state in GBM patients. METHODS: Standardized 3D brain MRI studies were performed, and contrast enhancing portions of each tumor were segmented and analyzed blinded to clinical state using principal component analysis (PCA), medial axis transformation (MAT), and coverage analysis. Associations between the 3D characteristics of the post-gadolinium enhanced regions and the clinical status of patients were performed. RESULTS: A total of 15 GBM patients (male: 11 (73%); median age (range): 62 years (36–72 years)) with a median disease duration of 6 months (range: 2–24 months) were studied cross-sectionally with 6 (40%) patients identified with tumor progression. Post-gadolinium features corresponding to the group with progressive disease exhibited a more spherical and symmetric shape relative to their stable counterparts (p

Published
2018

8. LGG-32. EVALUATION OF PEDIATRIC GLIOMA OUTCOME USING INTRAOPERATIVE MRI: A COHORT STUDY USING I-MiND (IMRIS MULTICENTER iMRI NEUROSURGERY DATABASE)

Author

Mark G. Hamilton, Douglas L. Brockmeyer, Richard A Roberts, Walter Hader, Samuel H. Cheshier, Jennifer Strahle, Michael Karsy, Robert J. Bollo, Ann-Christine Duhaime, Matthew D. Smyth, David J. Donahue, David D. Limbrick, Yves Starreveld, Eric C. Leuthardt, John Honeycutt, Daniel R. Hansen, John J. Evans, Jeffrey R. Leonard, Clair Gallagher, Michael R. Chicoine, Garnette R. Sutherland, John R. W. Kestle, S. Hassan Akbari, and Randy L. Jensen

Subjects
Cancer Research, medicine.medical_specialty, Intra operative, business.industry, Interventional magnetic resonance imaging, medicine.disease, Intraoperative MRI, Abstracts, Oncology, Glioma, Pediatric glioma, Medicine, Neurology (clinical), Progression-free survival, Neurosurgery, Radiology, business, Cohort study
Abstract

INTRODUCTION: Gliomas in pediatric patients remain challenging to treat. Intraoperative MRI (iMRI) may be a method to improve resection volumes, avoid critical structures, and guide intraoperative therapy in real-time. METHODS: We analyzed pediatric patients (age ≤18 years) in the I-MiND (IMRIS Multicenter iMRI Neurosurgery Database) who underwent resection of pathology-confirmed gliomas. RESULTS: A total of 327 patients (mean age 9.7 ± 4.6, 56.3% male) were identified who underwent treatment (13 neurosurgeons; 5 academic centers). Most tumors were World Health Organization (WHO) grade I (63.3%) without prior resection (82.6%) and were 31.7 ± 21.4 mm in average largest dimension. Of the 300 patients that underwent iMRI, additional tumor was resected from 140 patients (42.8%). Of the 37 patients with specimen sent to pathology after iMRI, 33 show positive tumor pathology (89.2%). The average surgery and room times were 5.6 ± 2.1 and 7.6 ± 2.2 hours, respectively. Mean overall survival (OS) for WHO grade I, II, III, and IV tumors was 35.4 ± 31.2, 20.1 ± 18.6, 19.2 ± 11.4, and 10.1 ± 10.6 months, respectively. On survival analysis, WHO grade and extent of resection impacted both OS and progression free survival (p

Published
2018

9. Identification and replication of prediction models for ovulation, pregnancy and live birth in infertile women with polycystic ovary syndrome

Author

Peter Casson, Valerie L. Baker, Gregory M. Christman, Scott Lucidi, Karl R. Hansen, Hongying Kuang, Rebecca S. Usadi, Michael P. Diamond, Hao Huang, Heping Zhang, G. Wright Bates, Susan Jin, Ruben Alvero, Christos Coutifaris, Richard S. Legro, Esther Eisenberg, and Nanette Santoro

Subjects
Infertility, Adult, Ovulation, medicine.medical_specialty, Logistic regression, law.invention, Randomized controlled trial, law, medicine, Humans, Randomized Controlled Trials as Topic, Gynecology, Pregnancy, business.industry, Free androgen index, Obstetrics, Rehabilitation, Obstetrics and Gynecology, Secondary data, Original Articles, Models, Theoretical, medicine.disease, Prognosis, Polycystic ovary, Reproductive Medicine, Fertilization, Female, Live birth, business, Infertility, Female, Live Birth, Polycystic Ovary Syndrome
Abstract

Study question Can we build and validate predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS)? Summary answer We were able to develop and validate a predictive model for pregnancy outcomes in women with PCOS using simple clinical and biochemical criteria particularly duration of attempting conception, which was the most consistent predictor among all considered factors for pregnancy outcomes. What is known already Predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome have been reported, but such models require validation. Study design, size, and duration This is a secondary analysis of the data from the Pregnancy in Polycystic Ovary Syndrome I and II (PPCOS-I and -II) trials. Both trials were double-blind, randomized clinical trials that included 626 and 750 infertile women with PCOS, respectively. PPCOS-I participants were randomized to either clomiphene citrate (CC), metformin, or their combination, and PPCOS-II participants to either letrozole or CC for up to five treatment cycles. Participants/materials, setting, and methods Linear logistic regression models were fitted using treatment, BMI, and other published variables as predictors of ovulation, conception, clinical pregnancy, and live birth as the outcome one at a time. We first evaluated previously reported significant predictors, and then constructed new prediction models. Receiver operating characteristic (ROC) curves were constructed and the area under the curves (AUCs) was calculated to compare performance using different models and data. Chi-square tests were used to examine the goodness-of-fit and prediction power of logistic regression model. Main results and the role of chance Predictive factors were similar between PPCOS-I and II, but the two participant samples differed statistically significantly but the differences were clinically minor on key baseline characteristics and hormone levels. Women in PPCOS-II had an overall more severe PCOS phenotype than women in PPCOS-I. The clinically minor but statistically significant differences may be due to the large sample sizes. Younger age, lower baseline free androgen index and insulin, shorter duration of attempting conception, and higher baseline sex hormone-binding globulin significantly predicted at least one pregnancy outcome. The ROC curves (with AUCs of 0.66-0.76) and calibration plots and chi-square tests indicated stable predictive power of the identified variables (P-values ≥0.07 for all goodness-of-fit and validation tests). Limitations, reasons for caution This is a secondary analysis. Although our primary objective was to confirm previously reported results and identify new predictors of ovulation and pregnancy outcomes among PPCOS-II participants, our approach is exploratory and warrants further replication. Wider implications of the findings We have largely confirmed the predictors that were identified in the PPCOS-I trial. However, we have also revealed new predictors, particularly the role of smoking. While a history of ever smoking was not a significant predictor for live birth, a closer look at current, quit, and never smoking revealed that current smoking was a significant risk factor. Study funding/competing interests The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD27049, U10 HD38992, U10HD055925, U10 HD39005, U10 HD33172, U10 HD38998, U10 HD055936, U10 HD055942, and U10 HD055944; and U54-HD29834. Heilongjiang University of Chinese Medicine Grants 051277 and B201005. R.S.L. reports receiving consulting fees from Euroscreen, AstraZeneca, Clarus Therapeutics, and Takeda, and grant support from Ferring, Astra Zeneca, and Toba. K.R.H. reports receiving grant support from Roche Diagnostics and Ferring Pharmascience. G.C. reports receiving Honorarium and grant support from Abbvie Pharmaceuticals and Bayer Pharmaceuticals. M.P.D. holds equity from Advanced Reproductive Care Inc. and DS Biotech, receives fees from Advanced Reproductive Care Inc., Actamax, Auxogyn, ZSX Medical, Halt Medical, and Neomed, and receives grant support from Boehringer-Ingelheim, Abbott, and BioSante, Ferring Pharmaceuticals, and EMD Serono. H.Z. receives research support from the Chinese 1000-scholar plan. Others report no disclosures other than NIH grant support. Trial registration number PPCOS-I and -II were respectively registered at Clinicaltrials.gov: NCT00719186 and NCT00719186.

Published
2015

11. Evolutionary-conserved telomere-linked helicase genes of fission yeast are repressed by silencing factors, RNAi components and the telomere-binding protein Taz1

Author

Geneviève Thon, Klavs R. Hansen, and Pablo Tejero Ibarra

Subjects
Heterochromatin, Centromere, Telomere-Binding Proteins, Hydroxamic Acids, Article, Gene Expression Regulation, Enzymologic, Conserved sequence, Chromodomain, Evolution, Molecular, RNA interference, Gene Expression Regulation, Fungal, Sequence Homology, Nucleic Acid, Schizosaccharomyces, Genetics, Gene Silencing, Enzyme Inhibitors, Conserved Sequence, Repetitive Sequences, Nucleic Acid, Telomere-binding protein, Adenosine Triphosphatases, biology, Base Sequence, RecQ Helicases, fungi, DNA Helicases, Telomere, biology.organism_classification, Histone Deacetylase Inhibitors, Histone, Schizosaccharomyces pombe, biology.protein, RNA Interference, Schizosaccharomyces pombe Proteins, Transcription Factors
Abstract

In Schizosaccharomyces pombe the RNAi machinery and proteins mediating heterochromatin formation regulate the transcription of non-coding centromeric repeats. These repeats share a high sequence similarity with telomere-linked helicase (tlh) genes, implying an ancestral relationship between the two types of elements and suggesting that transcription of the tlh genes might be regulated by the same factors as centromeric repeats. Indeed, we found that mutants lacking the histone methyltransferase Clr4, the Pcu4 cullin, Clr7 or Clr8, accumulate high levels of tlh forward and reverse transcripts. Mutations and conditions perturbing histone acetylation had similar effects further demonstrating that the tlh genes are normally repressed by heterochromatin. In contrast, mutations in the RNAi factors Dcr1, Ago1 or Rdp1 led only to a modest derepression of the tlh genes indicating an alternate pathway recruits heterochromatin components to telomeres. The telomere-binding protein Taz1 might be part of such a redundant pathway, tlh transcripts being present at low levels in Deltataz1 mutants and at higher levels in Deltataz1 Deltadcr1 double mutants. Surprisingly, the chromodomain protein Chp1, a component of the Ago1-containing RITS complex, contributes more to tlh repression than Ago1, indicating the repressive effects of Chp1 are partially independent of RITS. The tlh genes are found in the subtelomeric regions of several other fungi raising the intriguing possibility of conserved regulation and function.

Published
2006

12. Contribution of persistent C-Jun N-terminal kinase activity to the survival of human vestibular schwannoma cells by suppression of accumulation of mitochondrial superoxides

Author

Wei Ying Yue, Frederick E. Domann, Marlan R. Hansen, Augusta Fernando, and J. Jason Clark

Subjects
MAPK/ERK pathway, Cancer Research, Blotting, Western, Apoptosis, Biology, Immunoenzyme Techniques, Superoxides, Cell Line, Tumor, Humans, Phosphorylation, Protein kinase A, Protein kinase B, Cell Proliferation, chemistry.chemical_classification, Reactive oxygen species, Kinase, Cell growth, JNK Mitogen-Activated Protein Kinases, Neuroma, Acoustic, Molecular biology, Cell biology, Mitochondria, Oncology, chemistry, Basic and Translational Investigations, Neurology (clinical), Signal transduction, Mitogen-Activated Protein Kinases, Reactive Oxygen Species, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract

Vestibular schwannomas (VSs) result from inactivating mutations in the merlin tumor suppressor gene. The merlin protein suppresses a variety of progrowth kinase-signaling cascades, including extracellular regulated kinase/mitogen-activated protein kinase (ERK/MAPK), c-Jun N-terminal kinase (JNK), and phosphatidyl-inositol 3-kinase (PI3-K)/Akt. Recent studies indicate that ERKs and Akt are active in human VSs, and here we show that JNKs are also persistently active in human VS cells. With use of cultures of human VSs, we investigated the contribution of each of these signals to the proliferative and survival response of VS cells. Inhibition of ERK or Akt signaling reduced VS cell proliferation but did not increase apoptosis, whereas inhibition of JNK with SP600125, I-JIP, or siRNA knock-down reduced VS cell proliferation and survival by inducing apoptosis. By contrast, JNK activity promotes apoptosis in normal Schwann cells. Inhibition of JNK increased the fluorescence intensity of VS cells loaded with 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (H(2)DCFDA), a fluorescent probe for reactive oxygen species (ROS). Furthermore, ebselen, a ROS scavenger, rescued VS cells with suppressed JNK from apoptosis, suggesting that JNK activity protects VS cells from apoptosis by limiting accumulation of ROS. VS cultures treated with JNK inhibitors demonstrated significantly higher levels of MitoSOX Red fluorescence, implying that persistent JNK activity specifically suppresses superoxide production in the mitochondria. Overexpression of superoxide dismutase 2 (MnSOD; mitochondrial SOD) prevented apoptosis in VS cells with suppressed JNK signaling. Taken together, these results indicate that persistent JNK activity enhances VS cell survival, at least in part, by suppressing accumulation of mitochondrial superoxides.

Published
2011

13. Gut Microbial Signatures in Pediatric Crohn's Disease Vary According to Disease Activity Measures and Are Influenced by Proxies of Gastrointestinal Transit Time: An ImageKids Study.

Author

Nichols B, Russell RK, Short B, Papadopoulou R, Focht G, Ijaz UZ, Walters TD, Sladek M, Hansen R, Mack DR, Wine E, Griffiths AM, Turner D, and Gerasimidis K

Abstract

Introduction: We investigated relationships between disease activity measures and the gut microbiome in children with Crohn's disease (CD) and how these were confounded by gastrointestinal transit time., Methods: Microbiome was profiled (16S rRNA sequencing) in feces from 196 children with CD. Sixty participants also provided samples after 18 months. Mural inflammation (Pediatric Inflammatory Crohn's Magnetic Resonance Enterography Index, PICMI), the simple endoscopic score for CD, and the weighted pediatric Crohn's disease activity index (wPCDAI) were assessed. Fecal calprotectin, plasma C-reactive protein (CRP), and fecal water content (FWC), a proxy of gastrointestinal transit time, were measured too., Results: Microbiome α diversity, clustering, and differential taxa were related to disease status, but varied remarkably by disease activity measure used. The strongest relationships between microbiome and disease activity status were observed using wPCDAI; fewer or no relationships were seen using more objective measures like PICMI. Taxa predictive of disease activity status were dependent on the disease activity measure used with negligible overlap. Active disease was associated with more pathobionts (eg, Viellonella, Enterobacterales) and fewer fiber-fermenting organisms. The effect FWC had on microbiome superseded the effect of active disease for all disease activity measures, particularly with wPCDAI. Accounting for FWC, the differences in microbial signatures explained by disease activity status were attenuated or lost., Conclusions: In CD, microbiome signatures fluctuate depending on the measure used to assess disease severity; several of these signals might be secondary disease effects linked with changes in gut motility in active disease. PICMI appears to be less influenced when studying relationships between microbiome and mural inflammation in CD., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Published
2024
Full Text
View/download PDF

14. The circulating methylome in childhood-onset inflammatory bowel disease.

Author

Noble A, Adams A, Nowak J, Cheng G, Nayak K, Quinn A, Kristiansen M, Kalla R, Ventham NT, Giachero F, Jayamanne C, Hansen R, Hold GL, El-Omar E, Croft NM, Wilson D, Beattie RM, Ashton JJ, Zilbauer M, Ennis S, Uhlig HH, and Satsangi J

Abstract

The genetic contribution to inflammatory bowel disease (IBD) encompassing both Crohn's disease (CD) and ulcerative colitis (UC), accounts for around 20% of disease variance, highlighting the need to characterise environmental and epigenetic influences. Recently considerable progress has been made in characterising the adult methylome, in epigenome-wide association studies. We report detailed analysis of the circulating methylome in 86 patients with childhood-onset CD,UC and 30 controls using the Illumina Infinium Human MethylationEPIC platform. We derive and validate a 4-probe methylation biomarker (RPS6KA2, VMP1, CFI and ARHGEF3), with specificity and high diagnostic accuracy for paediatric IBD in UK and North American cohorts (AUC 0.90-0.94). Significant epigenetic age acceleration is present at diagnosis, with the greatest observed in CD patients. Cis-MeQTL analysis identifies genetic determinants underlying epigenetic alterations notably within the HLA 6p22.1-p21.33 region. Passive smoking exposure is associated with the development of UC rather than CD contrary to previous findings. These data provide new insights into epigenetic alterations in IBD and illustrate the reproducibility and translational potential of epigenome-wide association studies in complex diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Published
2024
Full Text
View/download PDF

15. Pediatric Inflammatory Bowel Disease Type Unclassified: A Nationwide Cohort Study in Scotland With up to 20 Years Follow-up Shows Reclassification in the Majority and Mild Course in Those Whose Diagnosis Is Unchanged.

Author

Wands DIF, Gianolio L, Cameron F, Hansen R, Russell RK, and Wilson DC

Abstract

Background: Given the paucity of long-term longitudinal data for inflammatory bowel disease type unclassified (IBDU), we aimed to clarify IBDU disease course and reclassification rate by presenting nationwide data with up to 20 years of follow-up., Methods: We analyzed a prospectively identified 11-year cohort of pediatric patients diagnosed with IBDU between January 1, 2003 and December 31, 2013 at all Scottish pediatric IBD centers and followed up into adult services until December 31, 2022. Data were obtained from electronic medical records at fixed timepoints (5 and 10 years post-diagnosis) and at the final follow-up., Results: Overall, 102 patients were included in the analysis (57/102 [56%] male, median [interquartile range {IQR}] age at diagnosis: 11.5 [9.1-13.2] years) with a median (IQR) follow-up length of 10.5 (8.6-14.0) years. A change of diagnosis was made in 61 of 102 patients (60%); of these, 30 patients (29%) were reclassified to Crohn's disease (CD) and 31 patients (30%) to ulcerative colitis (UC). Patients who remained with IBDU had higher 1- to 5-year remission rates (IBDU 30/39 [77%] vs reclassified 16/57 [28%], P < .05), with lower rates of moderate-to-severe disease (IBDU 3/39 [8%] vs reclassified 31/57 [54%], P < .05) and less need for biologics across all timepoints (IBDU vs reclassified: first timepoint 1/39 [3%] vs 17/57 [30%], second timepoint 1/33 [3%] vs 26/56 [46%], third timepoint 0/18 [0%] vs 16/33 [49%]; all P < .05). Higher rates of surgical resections were observed in reclassified patients (reclassified 11/61 [18%] vs IBDU 1/41 [2%], P = .02)., Conclusions: In our nationwide pediatric IBDU cohort, 60% of patients were reclassified to either UC or CD over 10.5 years of median follow-up; those who remained with IBDU had a milder disease course., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
Full Text
View/download PDF

16. Nationwide Real-World Exclusive Enteral Nutrition Practice Over Time: Persistence of Use as Induction for Pediatric Crohn's Disease and Emerging Combination Strategy With Biologics.

Author

Wands DIF, Gianolio L, Wilson DC, Hansen R, Chalmers I, Henderson P, Gerasimidis K, and Russell RK

Subjects
Humans, Male, Female, Child, Adolescent, Retrospective Studies, Scotland epidemiology, Remission Induction, SARS-CoV-2, Crohn Disease therapy, Enteral Nutrition statistics & numerical data, Enteral Nutrition methods, COVID-19 epidemiology, Biological Products therapeutic use
Abstract

Background: Exclusive enteral nutrition (EEN) is the recommended first-line induction treatment in pediatric patients with active luminal Crohn's disease (CD). We aimed to provide a nationwide overview of evolving EEN practices during an era of increasing biologic use., Methods: We analyzed a prospectively identified nationwide cohort of newly diagnosed pediatric patients with CD in Scotland between January 1, 2015, and June 30, 2022. Patients who received EEN for any indication were divided into 6-monthly epochs and examined over time. Differences during the COVID-19 pandemic (March 16, 2020, to July 19, 2021) were examined. Data were retrospectively collected from electronic medical records: demographics, anthropometrics, concomitant treatments, aspects of EEN administration, and remission/response rates. Descriptive statistics and linear regression were used for analyses., Results: A total of 649 patients with CD were identified (63% male; median age 12.6 [interquartile range, 10.8-14.8] years); 497 (77%) of 649 received EEN as postdiagnosis induction therapy with a median course length of 7.7 (interquartile range, 5.9-8.0) weeks. Including repeat courses, 547 EEN courses were examined. An increasing incidence of CD was observed over time with no significant changes in EEN usage, remission or response rates, nasogastric tube usage, or course completion (all P > .05). Increasing use of EEN combined with biologics (combination induction) as first-line induction was observed over time (P < .001). Considering COVID-19, lower rates of EEN usage were observed (P = .008) with no differences in remission, oral administration, and course completion rates (all P > .05)., Conclusions: Over the past 7.5 years, except during the COVID-19 pandemic, EEN usage rates have not changed despite an increase in biologic use, although combination induction is an emerging trend., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
Full Text
View/download PDF

17. Treatment of Active Crohn's Disease With Exclusive Enteral Nutrition Diminishes the Immunostimulatory Potential of Fecal Microbial Products.

Author

Kerbiriou C, Dickson C, Nichols B, Logan M, Mascellani A, Havlik J, Russell RK, Hansen R, Milling S, and Gerasimidis K

Abstract

Background: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN., Methods: Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing., Results: Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae&#95;UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi., Conclusions: This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Published
2024
Full Text
View/download PDF

18. Inflammation-related Proteins Support Diagnosis of Inflammatory Bowel Disease and Are Modified by Exclusive Enteral Nutrition in Children With Crohn's Disease, Especially of Ileal Phenotype.

Author

White B, Svolos V, Gervais L, Jatkowska A, Nichols B, MacDonald J, Seenan JP, Hansen R, Russell RK, Milling S, and Gerasimidis K

Abstract

Background: The immunological effects of treatment with exclusive enteral nutrition (EEN) in Crohn's disease (CD) remain unknown. We characterized the plasma levels of inflammation-related proteins (IRPs) in children with CD and ulcerative colitis (UC) compared with noninflammatory controls (non-IBD) and explored the effect of EEN in CD., Methods: Ninety-two IRPs were quantified using Olink proteomics in children with CD (n = 53), UC (n = 11), and non-IBD (n = 19). For 18 children with active CD, IRPs were measured before and after 8 weeks of EEN. Relationships with disease phenotype and response to EEN were studied., Results: Compared with non-IBD, patients with active UC and CD had different levels of 27 (24 raised, 3 decreased) and 29 (26 raised, 3 decreased) IRPs, respectively. Exclusive enteral nutrition modified the levels of 19 IRPs (13 increased, 6 decreased including CCL23, interleukin-24, interleukin-6, and MMP-1). More pronounced changes in IRP profile were observed in patients with ileal involvement and a ≥50% decrease in fecal calprotectin during EEN compared with those with colonic involvement and a <50% decrease in fecal calprotectin, respectively. A machine-learning model utilizing baseline IRP profile predicted response to EEN with a sensitivity of 89%, specificity of 57%, and accuracy of 73%. Thymic stromal lymphopoietin was the most important IRP in the model, this being higher in responders., Conclusions: Inflammation-related proteins may be useful in the differential diagnosis of IBD. Exclusive enteral nutrition extensively modulated IRPs levels in children with active CD with more pronounced effects observed in patients who showed a reduction in FC and had ileal disease involvement., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Published
2024
Full Text
View/download PDF

19. YouTube as a Source of Information for Food, Diet-Related Items, and Advisory Comments for the Management of Inflammatory Bowel Disease.

Author

Gkikas K, Wan M, Svolos V, Nichols B, Hansen R, Russell RK, and Gerasimidis K

Subjects
Humans, Diet, Social Media, Inflammatory Bowel Diseases therapy, Colitis, Ulcerative, Crohn Disease
Abstract

Background: Patients with inflammatory bowel disease (IBD) often use the Internet to seek information beyond that received from healthcare professionals. This study assessed the perceptions of YouTube presenters on the role of diet in the management of IBD., Methods: Videos discussing dietary aspects (food, diet-related items, and advisory comments [FODRIACs]) in the management of IBD were included. The perceptions of presenters toward each FODRIAC were labeled as positive, negative, or neutral/intermediate, and FODRIACs were classified according to their underlying role in the management of IBD (eg, symptom management, gut inflammation). Subgroup analysis was performed by type of video presenter (patients vs healthcare professionals), type of IBD (Crohn's disease vs ulcerative colitis), and reporting of scientific evidence supporting presenters' perceptions., Results: We identified 122 FODRIACs within 160 videos. Patient videos received a higher number of likes (median 85 [interquartile range, 35-156]) than healthcare professional videos (median 44 [interquartile range, 16-1440]) (P = .01). Scientific evidence was cited in 2 (3%) of 76 patient videos compared with 25 (35%) of 71 healthcare professional videos (P < .001). Positive perceptions were expressed about avocadoes, salmon, bananas, white bread, and rice, whereas negative perceptions were reported for processed, high-fat and high-sugar foods and carbonated drinks. Fewer negative perceptions were expressed in videos supported by scientific evidence than in videos that lacked evidence (scientific: 4 positive, 0 negative vs nonscientific: 7 positive, 20 negative; P = .01)., Conclusions: We have identified FODRIACs proposed as beneficial or detrimental in the management of IBD. The effect this information has on dietary practice as patients with IBD self-manage their condition needs further exploration., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Published
2024
Full Text
View/download PDF

20. Development and Validation of the Glasgow Exclusive Enteral Nutrition Index of Compliance.

Author

Jatkowska A, White B, Nichols B, Svolos V, Gkikas K, Hansen R, Russell RK, Gaya D, Brownson E, Seenan JP, Milling S, MacDonald J, and Gerasimidis K

Abstract

Background and Aims: Treatment adherence is key to the efficacy of exclusive enteral nutrition [100% EN] in active Crohn's disease [CD], but there are no biomarkers to objectively estimate this. We explored faecal parameters as biomarkers of compliance with 100% EN, and subsequently developed and validated the Glasgow Exclusive Enteral Nutrition Index of Compliance [GENIE]., Methods: Healthy adults replaced all [100% EN] or part [85% EN, 50% EN, 20% EN] of their diet with a formula for 7 days. Faecal pH, water content, short chain fatty acids, and branched chain fatty acids [BCFAs] were measured before [D0] and after [D7] each intervention. Optimal biomarkers and threshold values were derived using receiver operating characteristic curve analyses and machine learning to develop the GENIE. The GENIE was then validated in 30 CD children, during and after 100% EN., Results: In all, 61 adults were recruited. D7 faecal pH and the ratios of BCFAs to either acetate or butyrate performed the best to differentiate between patients on 100% EN from <100% EN. Two models were generated; one included faecal metabolites (Laboratory GENIE, L-GENIE; sensitivity, specificity, and positive predictive value [PPV] of 88%, 94%, and 92%) and a second one [Clinical Genie, C-GENIE] which considers only faecal pH [sensitivity, specificity, and PPV of 84%, 86%, and 81%]. Validation of GENIE in CD children found that C-GENIE outperformed L-GENIE, producing a sensitivity, specificity, and PPV of 85%, 88%, and 88%, respectively., Conclusions: GENIE can help predict adherence to 100% EN and may complement current conventional dietary assessment., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Published
2023
Full Text
View/download PDF

21. Thromboprophylaxis Use in Paediatric Inflammatory Bowel Disease: An International RAND Appropriateness Panel.

Author

Torrente F, Meade S, Benchimol EI, de Ridder L, Croft NM, Kammermeier J, Mack DR, Klomberg RCW, Turner D, Wilson DC, Martín-de-Carpi J, Bronsky J, Amil Dias J, Walker G, van Ommen CH, Powar MP, Burgess N, Irving PM, Samaan MA, and Hansen R

Subjects
Humans, Anticoagulants therapeutic use, Venous Thromboembolism, Inflammatory Bowel Diseases drug therapy, Crohn Disease therapy, Colitis, Ulcerative therapy
Abstract

Background and Aims: Thromboprophylaxis use in paediatric inflammatory bowel disease [IBD] is inconsistent. Current guidelines only support treating children with acute severe colitis with risk factors. We convened an international RAND panel to explore thromboprophylaxis in paediatric IBD inpatients in the context of new evidence., Methods: We convened a geographically diverse 14-person panel of paediatric gastroenterologists alongside supporting experts. An online survey was sent before an online meeting. Panellists were asked to rate the appropriateness of thromboprophylaxis in hospitalised paediatric IBD patients via 27 scenarios of varying ages, gender, and phenotype, with and without thrombotic risk factors. Anonymised results were presented at the meeting. A second modified survey was distributed to all panellists present at the meeting. Results from the second survey constitute the RAND panel results. The validated RAND disagreement index defined disagreement when ≥ 1., Results: The combined outcome of thromboprophylaxis being considered appropriate until discharge and inappropriate to withhold was seen in 20 of 27 scenarios, including: all patients with new-onset acute severe colitis; all flares of known ulcerative colitis, irrespective of risk factors except in pre-pubescent patients with limited disease and no risk factors; and all Crohn's patients with risk factors. Disagreement was seen in five scenarios regarding Crohn's without risk factors, where outcomes were already uncertain., Conclusions: RAND panels are an established method to assess expert opinion in areas of limited evidence. This work therefore constitutes neither a guideline nor a consensus; however, the findings suggest a need to re-evaluate the role of thromboprophylaxis in future guidelines., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Published
2022
Full Text
View/download PDF

22. Venous Thromboembolism in Children with Inflammatory Bowel Disease: When is the Right Time for Thromboprophylaxis?

Author

Torrente F and Hansen R

Subjects
Anticoagulants therapeutic use, Child, Cohort Studies, Humans, Incidence, Prospective Studies, Registries, Inflammatory Bowel Diseases complications, Inflammatory Bowel Diseases drug therapy, Venous Thromboembolism epidemiology, Venous Thromboembolism etiology, Venous Thromboembolism prevention & control, Venous Thrombosis epidemiology, Venous Thrombosis etiology, Venous Thrombosis prevention & control
Published
2022
Full Text
View/download PDF

23. The Dockstore: enhancing a community platform for sharing reproducible and accessible computational protocols.

Author

Yuen D, Cabansay L, Duncan A, Luu G, Hogue G, Overbeck C, Perez N, Shands W, Steinberg D, Reid C, Olunwa N, Hansen R, Sheets E, O'Farrell A, Cullion K, O'Connor BD, Paten B, and Stein L

Subjects
Cloud Computing, Computational Biology education, Data Visualization, Humans, National Heart, Lung, and Blood Institute (U.S.), National Human Genome Research Institute (U.S.), Reproducibility of Results, United States, Computational Biology methods, Information Dissemination, Internet, Software, Workflow
Abstract

Dockstore (https://dockstore.org/) is an open source platform for publishing, sharing, and finding bioinformatics tools and workflows. The platform has facilitated large-scale biomedical research collaborations by using cloud technologies to increase the Findability, Accessibility, Interoperability and Reusability (FAIR) of computational resources, thereby promoting the reproducibility of complex bioinformatics analyses. Dockstore supports a variety of source repositories, analysis frameworks, and language technologies to provide a seamless publishing platform for authors to create a centralized catalogue of scientific software. The ready-to-use packaging of hundreds of tools and workflows, combined with the implementation of interoperability standards, enables users to launch analyses across multiple environments. Dockstore is widely used, more than twenty-five high-profile organizations share analysis collections through the platform in a variety of workflow languages, including the Broad Institute's GATK best practice and COVID-19 workflows (WDL), nf-core workflows (Nextflow), the Intergalactic Workflow Commission tools (Galaxy), and workflows from Seven Bridges (CWL) to highlight just a few. Here we describe the improvements made over the last four years, including the expansion of system integrations supporting authors, the addition of collaboration features and analysis platform integrations supporting users, and other enhancements that improve the overall scientific reproducibility of Dockstore content., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2021
Full Text
View/download PDF

24. Biomarkers predictive of late cardiogenic shock development in patients with suspected ST-elevation myocardial infarction.

Author

Frydland M, Møller JE, Lindholm MG, Hansen R, Wiberg S, Lerche Helgestad OK, Thomsen JH, Goetze JP, Engstrøm T, Frikke-Schmidt R, Ravn HB, Holmvang L, Jensen LO, Kjaergaard J, and Hassager C

Subjects
Aged, Biomarkers blood, Female, Follow-Up Studies, Humans, Male, Prognosis, ROC Curve, Retrospective Studies, ST Elevation Myocardial Infarction complications, Shock, Cardiogenic etiology, Atrial Natriuretic Factor blood, Natriuretic Peptide, Brain blood, ST Elevation Myocardial Infarction blood, Shock, Cardiogenic blood
Abstract

Background: Cardiogenic shock complicating ST-elevation myocardial infarction is characterised by progressive left ventricular dysfunction causing inflammation and neurohormonal activation. Often, cardiogenic shock develops after hospital admission. Whether inflammation and a neurohormonal activation precede development of clinical cardiogenic shock is unknown., Methods and Results: In 93% of 2247 consecutive patients with suspected ST-elevation myocardial infarction admitted at two tertiary heart centres, admission plasma levels of pro-atrial natriuretic peptide, copeptin, mid-regional pro-adrenomedullin and stimulation-2 were measured on hospital admission. Patients were stratified according to no cardiogenic shock development and cardiogenic shock developed before (early cardiogenic shock) or after (late cardiogenic shock) leaving the catheterization laboratory. In total, 225 (10%) patients developed cardiogenic shock, amongst these patients late cardiogenic shock occurred in 64 (2.9%). All four biomarkers were independently associated with the development of late cardiogenic shock (odds ratio per two-fold increase in risk: 1.19-3.13) even when adjusted for the recently developed Observatoire Régional Breton sur l'Infarctus risk score for prediction of late cardiogenic shock development. Furthermore, pro-atrial natriuretic peptide, copeptin and mid-regional pro-adrenomedullin, but not stimulation-2, added significant predictive information, when added to the Observatoire Régional Breton sur l'Infarctus risk score (area under the receiver-operating characteristic curve, pro-atrial natriuretic peptide: 0.87, p =0.0008; copeptin: 0.86, p <0.05; mid-regional pro-adrenomedullin: 0.88, p =0.006)., Conclusions: Pro-atrial natriuretic peptide, copeptin, mid-regional pro-adrenomedullin and stimulation-2 admission plasma concentration were associated with late cardiogenic shock development in patients admitted with suspected ST-elevation myocardial infarction. Pro-atrial natriuretic peptide, mid-regional pro-adrenomedullin and copeptin had independent predictive value for late cardiogenic shock development.

Published
2020
Full Text
View/download PDF

25. A Decade of Varicella Screening Within a Paediatric Inflammatory Bowel Disease Population.

Author

Harris RE, Curtis L, Hegde V, Garrick V, Gervais L, Armstrong L, Delahunty C, Eccleston A, Al-Hourani G, Flynn DM, Merrick V, Barclay AR, Tayler R, Hansen R, and Russell RK

Subjects
Anti-Inflammatory Agents therapeutic use, Antibodies, Viral blood, Chickenpox blood, Chickenpox complications, Child, Female, Hospitalization statistics & numerical data, Humans, Immunocompromised Host, Immunoglobulin G blood, Immunosuppressive Agents therapeutic use, Induction Chemotherapy, Male, Opportunistic Infections blood, Opportunistic Infections complications, Post-Exposure Prophylaxis statistics & numerical data, Prednisolone therapeutic use, Retrospective Studies, Chickenpox diagnosis, Chickenpox prevention & control, Inflammatory Bowel Diseases drug therapy, Opportunistic Infections diagnosis, Opportunistic Infections prevention & control, Vaccination statistics & numerical data
Abstract

Introduction: Increased risk of opportunistic infection-e.g., varicella zoster infection-secondary to therapies is a cause of morbidity in inflammatory bowel disease [IBD] patients. The UK vaccination schedule does not include varicella immunisation. We aimed to evaluate the varicella screening and immunisation programme in a paediatric IBD population., Methods: Data regarding IBD diagnosis, varicella status, and consequent immunisations/treatment interventions were collected retrospectively from the records of patients diagnosed with IBD over a 10-year period [2009-2018]., Results: In all, 520 IBD patients were diagnosed; 505/520 [97%] had varicella testing; 46/505 [9%] were naïve. Of 501 patients, 391[78%] were tested before or within 7 days of diagnosis; this increased in the second 5-year period compared with the first (229/268 [85%] versus 162/233 [70%]; p <0.00001). Median diagnosis age of naïve patients was lower [8.3 years versus 12.8 years; p <0.00001]. Where vaccination was feasible, 21/31 [68%] had two and 7/31 [23%] one immunisation. Prednisolone induction led to lower rates of vaccination (5/13 [39%] versus 23/33 [70%] for other induction therapies; p =0.02). Of 28 vaccinated patients, 5 [18%] had suspected breakthrough varicella; and 6/18 [33%] unimmunised patients required post-exposure prophylaxis or treatment for varicella. Immunisation was associated with a decrease in patients requiring post-exposure prophylaxis (0/28 [0%] versus 5/18 [28%]; p =0.0006) and varicella-related hospital admission (1/28 [4%] versus 4/18 [22%]; p =0.01)., Conclusions: High rates of varicella screening and immunisation within a PIBD population are possible, resulting in a reduction in hospital admissions for varicella treatment. Varicella immunisation may be of increasing importance within the PIBD population with the emergence of novel therapeutic strategies., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2020
Full Text
View/download PDF

26. Risk factors of late cardiogenic shock and mortality in ST-segment elevation myocardial infarction patients.

Author

Obling L, Frydland M, Hansen R, Møller-Helgestad OK, Lindholm MG, Holmvang L, Ravn HB, Wiberg S, Thomsen JH, Jensen LO, Kjærgaard J, Møller JE, and Hassager C

Subjects
Denmark epidemiology, Follow-Up Studies, Hospital Mortality trends, Incidence, Patient Admission trends, Percutaneous Coronary Intervention, Prognosis, Prospective Studies, Risk Factors, ST Elevation Myocardial Infarction mortality, ST Elevation Myocardial Infarction surgery, Shock, Cardiogenic epidemiology, Survival Rate trends, Time Factors, Registries, ST Elevation Myocardial Infarction complications, Shock, Cardiogenic etiology
Abstract

Background: The incidence of cardiogenic shock (CS) in patients with ST-segment elevation myocardial infarction (STEMI) is as high as 10%. The majority of patients are thought to develop CS after admission (late CS), but the incidence in a contemporary STEMI cohort admitted for primary percutaneous intervention remains unknown., Aim: The aim of this study was to assess the incidence and time of CS onset in patients with suspected STEMI admitted in two high-volume tertiary heart centres and to assess the variables associated with the development of late CS., Methods: We included consecutive patients admitted for acute coronary angiography with suspected STEMI in a 1-year period. Cardiogenic shock was based on clinical criteria and subdivided into patients with shock on admission, patients developing shock during catheterisation and patients developing shock later during hospitalisation. Follow-up for all-cause mortality was done using registries., Results: A total of 2247 patients with suspected STEMI were included, whereof 225 (10%) developed CS. The majority (56%) had CS on admission, 16% developed CS in the catheterisation laboratory and 28% developed late CS. Thirty-day mortality was 3.1% versus 47% in non-CS versus CS patients ( p logrank < 0.0001). Age, stroke, time from symptom onset to intervention, anterior STEMI, heart rate/systolic blood pressure ratio and being comatose after resuscitation from cardiac arrest were independently associated with the development of late CS., Conclusion: In this study, 10% of patients admitted with suspected STEMI for acute coronary angiography presented with or developed CS. Most were in shock on admission. Irrespective of the timing of shock, mortality was high.

Published
2018
Full Text
View/download PDF

27. Genital Granulomatosis in Male and Female Patients With Crohn's Disease: Clinical Presentation and Treatment Outcomes.

Author

Dederichs F, Iesalnieks I, Sladek M, Tzivinikos C, Hansen R, Muñoz C, Pavli P, Cavicchi M, Abitbol V, Rahier JF, Vavricka S, Katsanos K, and Domènech E

Subjects
Adolescent, Adrenal Cortex Hormones therapeutic use, Adult, Aged, Asymptomatic Diseases, Child, Crohn Disease diagnosis, Crohn Disease drug therapy, Edema etiology, Female, Genital Diseases, Female drug therapy, Genital Diseases, Female pathology, Genital Diseases, Male pathology, Granuloma drug therapy, Granuloma pathology, Humans, Immunologic Factors therapeutic use, Male, Middle Aged, Retrospective Studies, Skin Ulcer etiology, Tumor Necrosis Factor-alpha antagonists & inhibitors, Young Adult, Colitis complications, Crohn Disease complications, Genital Diseases, Female etiology, Genital Diseases, Male etiology, Granuloma etiology, Ileitis complications
Abstract

Background: Genital granulomatosis [GG] is a metastatic form of Crohn's disease [CD], characterised by granulomatous inflammation of the genital skin without contact with the gastrointestinal tract. Little is known about GG, as most publications are case reports or small series, and only sporadic in male cases., Methods and Aims: Cases of GG were retrospectively collected through the Collaborative Network For Exceptionally Rare case reports project of the European Crohn's and Colitis Organisation., Results: A total of 43 patients [9 males, 34 females] were diagnosed as having GG, mostly as oedema and/or ulcers. Histological confirmation of granulomas was obtained in 70% of the cases. CD location was colonic or ileocolonic in 97% and perianal disease was documented in 57%. There was no significant difference between males and females in CD phenotype or genital lesions. GG was the first manifestation of inflammatory bowel disease [IBD] in one-third of the patients; these patients were younger at the time of GG occurrence and they all were non-smokers. GG occurred in the absence of gastrointestinal disease activity in 30% of the cases. Ten out of 11 patients [91%] responded to systemic corticosteroid treatment, 5/9 patients responded to immunomodulators, and 9/11 patients responded to anti-tumour necrosis factor alpha [TNF-α] agents., Conclusions: GG is a rare extraintestinal manifestation of CD. It mainly occurs among women, in the setting of colonic involvement of CD, and perianal disease is often associated. Most cases are successfully managed with systemic corticosteroids or anti-TNF agents., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Published
2018
Full Text
View/download PDF

28. Two-stage genome-wide methylation profiling in childhood-onset Crohn's Disease implicates epigenetic alterations at the VMP1/MIR21 and HLA loci.

Author

Adams AT, Kennedy NA, Hansen R, Ventham NT, OʼLeary KR, Drummond HE, Noble CL, El-Omar E, Russell RK, Wilson DC, Nimmo ER, Hold GL, and Satsangi J

Subjects
Adult, Case-Control Studies, Child, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genotype, HLA Antigens genetics, Humans, Male, Membrane Proteins genetics, MicroRNAs genetics, Prognosis, Biomarkers analysis, Crohn Disease genetics, DNA Methylation, Epigenesis, Genetic genetics, Genome, Human, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics
Abstract

Background: As a result of technological and analytical advances, genome-wide characterization of key epigenetic alterations is now feasible in complex diseases. We hypothesized that this may provide important insights into gene-environmental interactions in Crohn's disease (CD) and is especially pertinent to early onset disease., Methods: The Illumina 450K platform was applied to assess epigenome-wide methylation profiles in circulating leukocyte DNA in discovery and replication pediatric CD cohorts and controls. Data were corrected for differential leukocyte proportions. Targeted replication was performed in adults using pyrosequencing. Methylation changes were correlated with gene expression in blood and intestinal mucosa., Results: We identified 65 individual CpG sites with methylation alterations achieving epigenome-wide significance after Bonferroni correction (P < 1.1 × 10(-7)), and 19 differently methylated regions displaying unidirectional methylation change. There was a highly significant enrichment of methylation changes around GWAS single nucleotide polymorphisms (P = 3.7 × 10(-7)), notably the HLA region and MIR21. Two-locus discriminant analysis in the discovery cohort predicted disease in the pediatric replication cohort with high accuracy (area under the curve, 0.98). The findings strongly implicate the transcriptional start site of MIR21 as a region of extended epigenetic alteration, containing the most significant individual probes (P = 1.97 × 10(-15)) within a GWAS risk locus. In extension studies, we confirmed hypomethylation of MIR21 in adults (P = 6.6 × 10(-5), n = 172) and show increased mRNA expression in leukocytes (P < 0.005, n = 66) and in the inflamed intestine (P = 1.4 × 10(-6), n = 99)., Conclusions: We demonstrate highly significant and replicable differences in DNA methylation in CD, defining the disease-associated epigenome. The data strongly implicate known GWAS loci, with compelling evidence implicating MIR21 and the HLA region.

Published
2014
Full Text
View/download PDF

30. The evaluation of AZ66, an optimized sigma receptor antagonist, against methamphetamine-induced dopaminergic neurotoxicity and memory impairment in mice.

Author

Seminerio MJ, Hansen R, Kaushal N, Zhang HT, McCurdy CR, and Matsumoto RR

Subjects
Analysis of Variance, Animals, Avoidance Learning drug effects, Body Temperature drug effects, Disease Models, Animal, Dopamine Plasma Membrane Transport Proteins metabolism, Male, Memory Disorders etiology, Mice, Neurotoxicity Syndromes complications, Neurotoxicity Syndromes etiology, Neurotransmitter Agents pharmacokinetics, Protein Binding drug effects, Receptors, sigma antagonists & inhibitors, Recognition, Psychology drug effects, Tritium pharmacokinetics, Benzothiazoles therapeutic use, Dopamine metabolism, Dopamine Uptake Inhibitors toxicity, Memory Disorders drug therapy, Methamphetamine toxicity, Piperazines therapeutic use
Abstract

Sigma (σ) receptors have recently been identified as potential targets for the development of novel therapeutics aimed at mitigating the effects of methamphetamine. Particularly, σ receptors are believed to mitigate some of the neurotoxic effects of methamphetamine through modulation of dopamine, dopamine transporters and body temperature. Furthermore, recent evidence suggests that targeting σ receptors may prevent cognitive impairments produced by methamphetamine. In the present study, an optimized σ receptor antagonist, AZ66, was evaluated against methamphetamine-induced neurotoxicity and cognitive dysfunction. AZ66 was found to be highly selective for σ receptors compared to 64 other sites tested. Pretreatment of male, Swiss Webster mice with i.p. dosing of AZ66 significantly attenuated methamphetamine-induced striatal dopamine depletions, striatal dopamine transporter reductions and hyperthermia. Additionally, neurotoxic dosing with methamphetamine caused significant memory impairment in the object recognition test, which was attenuated when animals were pretreated with AZ66; similar trends were observed in the step-through passive avoidance test. Taken together, these results suggest that targeting σ receptors may provide neuroprotection against the neurotoxicity and cognitive impairments produced by methamphetamine.

Published
2013
Full Text
View/download PDF

31. Rising incidence of pediatric inflammatory bowel disease in Scotland.

Author

Henderson P, Hansen R, Cameron FL, Gerasimidis K, Rogers P, Bisset WM, Reynish EL, Drummond HE, Anderson NH, Van Limbergen J, Russell RK, Satsangi J, and Wilson DC

Subjects
Adolescent, Age Factors, Child, Child, Preschool, Female, Humans, Incidence, Infant, Male, Retrospective Studies, Scotland epidemiology, Sex Factors, Inflammatory Bowel Diseases epidemiology
Abstract

Background: An accurate indication of the changing incidence of pediatric inflammatory bowel disease (PIBD) within a population is useful in understanding concurrent etiological factors. We aimed to compare the current incidence and other demographic attributes of PIBD in the Scottish population to previous data., Methods: A national cohort of prospectively and retrospectively acquired incident cases of PIBD diagnosed less than 16 years old in pediatric services in Scotland was captured for the period 2003-2008; historical Scottish data were used for comparison (1990-1995). Age/sex-adjusted incidences were calculated and statistical comparisons made using Poisson regression., Results: During the 2003-2008 study period 436 patients were diagnosed with PIBD in Scotland, giving an adjusted incidence of 7.82/100,000/year. The incidence of Crohn's disease (CD) was 4.75/100,000/year, ulcerative colitis (UC) 2.06/100,000/year, and inflammatory bowel disease-unclassified (IBDU) 1.01/100,000/year. Compared with data from 1990-1995 when 260 IBD patients were diagnosed, significant rises in the incidence of IBD (from 4.45/100,000/year, P < 0.0001), CD (from 2.86/100,000/year, P < 0.0001), and UC (from 1.59/100,000/year, P = 0.023) were seen. There was also a significant reduction in the median age at IBD diagnosis from 12.7 years to 11.9 years between the periods (P = 0.003), with a continued male preponderance., Conclusions: The number of Scottish children diagnosed with IBD continues to rise, with a statistically significant 76% increase since the mid-1990 s. Furthermore, PIBD is now being diagnosed at a younger age. The reason for this continued rise is not yet clear; however, new hypotheses regarding disease pathogenesis and other population trends may provide further insights in future years., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Published
2012
Full Text
View/download PDF

32. Mobilization of hematopoietic progenitor cells by yeast-derived beta-glucan requires activation of matrix metalloproteinase-9.

Author

Cramer DE, Wagner S, Li B, Liu J, Hansen R, Reca R, Wu W, Surma EZ, Laber DA, Ratajczak MZ, and Yan J

Subjects
Animals, Bone Marrow Cells drug effects, Bone Marrow Cells enzymology, Bone Marrow Cells metabolism, Cell Differentiation drug effects, Chemokine CXCL12 blood, Complement Activation immunology, Complement C3 immunology, Cytokines metabolism, Enzyme Activation drug effects, Female, Granulocyte Colony-Stimulating Factor pharmacology, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells drug effects, Hematopoietic Stem Cells enzymology, Humans, Inflammation Mediators, Macrophage-1 Antigen immunology, Mice, Mice, Inbred C57BL, Recombinant Proteins, Hematopoietic Stem Cell Mobilization, Matrix Metalloproteinase 9 metabolism, Saccharomyces cerevisiae chemistry, beta-Glucans pharmacology
Abstract

Poly-(1,6)-beta-d-glucopyranosyl-(1,3)-beta-d-glucopyranose (PGG) beta-glucan is a soluble yeast-derived polysaccharide that has previously been shown to induce hematopoietic progenitor cell (HPC) mobilization. However, the mobilizing mechanism of action remains unknown. Here, we confirmed that PGG beta-glucan alone or in combination with granulocyte colony-stimulating factor (G-CSF) mobilizes HPC into the periphery. Optimal mobilizing effects were seen 24-48 hours after PGG beta-glucan doses of 4.8-9.6 mg/kg. Animals treated with G-CSF and PGG beta-glucan showed a collaborative effect in HPC mobilization compared with G-CSF treatment alone. Additional studies demonstrated that neither complement 3 nor complement receptor 3 played a role in this effect and that PGG beta-glucan treatment did not induce proinflammatory cytokine secretion. However, bone marrow cells from PGG beta-glucan-treated mice secreted abundant matrix metalloproteinase-9 (MMP-9), and PGG beta-glucan-induced HPC mobilization was abrogated in MMP-9 knockout mice. Moreover, we demonstrated that both hematopoietic and nonhematopoietic cells contributed to MMP-9 secretion upon PGG beta-glucan treatment. In addition, HPCs mobilized by PGG beta-glucan had similar levels of engraftment in host and lineage differentiation capability compared with those mobilized by G-CSF. Thus, PGG beta-glucan is an agent that enhances HPC mobilization and may improve the outcome of clinical stem cell transplantation.

Published
2008
Full Text
View/download PDF

33. Physiological and cognitive performance of soldiers conducting routine patrol and reconnaissance operations in the tropics.

Author

Amos D, Hansen R, Lau WM, and Michalski JT

Subjects
Acclimatization, Adult, Body Temperature, Body Weight, Energy Metabolism, Heart Rate, Heat Stress Disorders diagnosis, Heat Stress Disorders physiopathology, Heat Stress Disorders psychology, Humans, Male, Northern Territory, Water-Electrolyte Balance, Weight-Bearing, Cognition physiology, Heat Stress Disorders etiology, Military Personnel psychology, Psychomotor Performance physiology, Tropical Climate adverse effects
Abstract

The physiological and cognitive performance of acclimatized soldiers undertaking routine patrol and reconnaissance activities in the tropics was investigated. Data were obtained during a patrol and a reconnaissance exercise followed by a short assault. Ambient conditions were characterized by temperatures of 30 to 33 degrees C, low humidity (52-59%), and moderate to high solar radiation. Maximum metabolic rates during patrol were high, although the equipment carried was modest and the terrain was not severe. Rectal temperatures peaked at 38.2 and 38.4 degrees C for patrol and assault activities, respectively; peak heart rates were 160 beats min-1 for each activity. Sweat rates of approximately 9 and 14 g kg-1 body weight h-1 were recorded for patrol and assault activities, respectively. The soldiers maintained adequate hydration levels and displayed no evidence of deterioration in cognitive performance. The data show that routine operational activities in tropical conditions induced physiological strain in acclimatized soldiers. However, this strain was not maintained at hazardous levels for lengthy periods.

Published
2000

35. Antisporozoite antibodies in mice immunized with irradiation-attenuated Plasmodium berghei sporozoites.

Author

Hansen R, deSilva S, and Strickland GT

Subjects
Animals, Fluorescent Antibody Technique, Immunization, Malaria immunology, Malaria prevention & control, Male, Mice, Vaccines, Attenuated, Immunoglobulin G analysis, Immunoglobulin M analysis, Plasmodium berghei immunology
Abstract

Sera from NMRI/NIH mice were tested for the presence of IgM and IgG anti-sporozoite antibodies using the indirect fluorescent antibody test (IFAT). Both IgM and IgG antibody titres were related to the number of immunizations with irradition-attenuated Plasmodium berghei sporozoites, and protection from challenge with subsequent non-attenuated sporozoites correlated with the pre-challenge antibody titre. Sera taken five days following challenge showed marked reductions in antibody titres, except for the group receiving the maximum (four) immunizations. Groups immunized with frozen sporozoites or mosquito tissue antigen developed neither antibodies to sporozoites nor protective immunity; nor did animals infected with parasitized blood. However, sera from mice immunized four times with attenuated sporozoites demonstrated IFA titres to blood-stage antigens. The results show that both IgM and IgG antisporozoite antibodies could be detected in mice immunized with attenuated-sporozoites by IFAT, and that the antibody titres correlated with protective immunity. Cross reaction with blood-stage antigens occurred, but the test should still prove useful.

Published
1979
Full Text
View/download PDF

36. Properties of adaptive hexokinase isozymes of the rat.

Author

Hansen R, Pilkis SJ, and Krahl ME

Subjects
Adipose Tissue analysis, Animals, Cycloheximide pharmacology, DNA antagonists & inhibitors, Dactinomycin pharmacology, Diabetes Mellitus, Experimental chemically induced, Diet, Electrophoresis, Epididymis, Fasting, In Vitro Techniques, Insulin pharmacology, Male, Puromycin pharmacology, Rats, Hexokinase analysis, Liver enzymology
Published
1967
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results