tbuckley/cabot-search huggingface dataset:
Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance
Authors: Thomas E. Starzl, Anthony J. Demetris, Massimo Trucco, Noriko Murase, Camillo Ricordi, Suzanne Ildstad, Hector Ramos, Satoru Todo, Andreas Tzakis, John J. Fung, Michael Nalesnik, Adriana Zeevi, William A. Rudert, Mirjana Kocova
Journal: Hepatology (1993)

Improvements in the prevention or control of rejection of the kidney and liver have been largely interchangeable (1, 2) and then applicable, with very little modification, to thoracic and other organs.However, the mechanism by which anti rejection treatment permits any of these grafts to be "accepted" has been an immunological enigma (3, 4).We have proposed recently that the exchange of migratory leukocytes between the transplant and the recipient with consequent long-term cellular chimerism in both is the basis for acceptance of all whole-organ allografts and xenografts (5).Although such chimerism was demonstrated only a few months ago, the observations have increased our insight into transplantation immunology and have encouraged the development of alternative therapeutic strategies (6). DISCOVERY OF GRAFT CHIMERISM After Liver TransplantationSuccessful transplants were long envisioned as an alien patch in a homogeneous host (Fig. 1, left).The first unequivocal evidence that whole-organ grafts in human beings become genetic composites (chimeras) was obtained in 1969 with karyotyping studies in female recipients oflivers obtained from male cadaveric donors.Postoperatively, the hepatocytes and the endothelium of the major blood vessels of the grafts retained their donor sex, whereas the entire macrophage system, including the Kupffer cells, was replaced with recipient female cells (identified by their characteristic Barr bodies) within 100 days (7, 8) (Fig. 1, middle).These observations attracted considerable attention at the time, primarily
Response to Letters Regarding Article, “Mild Retinopathy Is a Risk Factor for Cardiovascular Mortality in Japanese With and Without Hypertension: The Ibaraki Prefectural Health Study”
Authors: Toshimi Sairenchi, Takashi Muto, Hiroyasu Iso, Kazumasa Yamagishi, Fujiko Irie, Yoshiro Okubo, Hitoshi Ota, Junko Gunji
Journal: Circulation (2012)
Experience With 2-Chlorodeoxyadenosine in Previously Untreated Children With Newly Diagnosed Acute Myeloid Leukemia and Myelodysplastic Diseases
Authors: R. A. Krance, C. A. Hurwitz, D. R. Head, S. C. Raimondi, F. G. Behm, K. R. Crews, D. K. Srivastava, H. Mahmoud, W. M. Roberts, X. Tong, R. L. Blakley, R. C. Ribeiro
Journal: Journal of Clinical Oncology (2001)

To develop more effective chemotherapy regimens for childhood acute myelogenous leukemia (AML).Between June 1991 and December 1996, we administered the nucleoside analog 2-chlorodeoxyadenosine (2-CDA) to 73 children with primary AML and 20 children with secondary AML or myelodysplastic syndrome (MDS). Patients received one or two 5-day courses of 2-CDA (8.9 mg/m(2)/d) given by continuous infusion. All patients then received one to three courses of daunomycin, cytarabine, and etoposide (DAV) remission induction therapy.Seventy-two patients with primary AML were assessable for response. Their rate of complete remission (CR) was 24% after one course of 2-CDA, 40% after two courses of 2-CDA, and 78% after DAV therapy. Of the 57 patients who entered CR, 11 subsequently underwent allogeneic bone marrow transplantation (BMT), and 40 underwent autologous BMT. Twenty-nine patients remain in continuous CR after BMT. Two patients remain in CR after chemotherapy only. The 5-year event-free survival (EFS) estimate was 40% (SE = 0.080%). Patients with French-American-British (FAB) M5 AML had a higher rate of CR after treatment with 2-CDA (45% after one course and 70.6% after two courses) than did others (P =.002). In contrast, no patient with FAB M7 AML (n = 10) entered CR after treatment with 2-CDA. Similarly, no patient with primary MDS (n = 6) responded to 2-CDA. Seven patients with secondary AML or MDS (n = 14) had a partial response to one course of 2-CDA.This agent was well tolerated, and its toxicity was acceptable. Future trials should examine the effectiveness of 2-CDA given in combination with other agents effective against AML.
Defining a Chromatin Pattern that Characterizes DNA-Hypermethylated Genes in Colon Cancer Cells
Authors: Kelly M. McGarvey, Leander Van Neste, Leslie Cope, Joyce E. Ohm, James G. Herman, Wim Van Criekinge, Kornel E. Schuebel, Stephen B. Baylin
Journal: Cancer Research (2008)

Epigenetic gene regulation is a key determinant of heritable gene expression patterns and is critical for normal cellular function. Dysregulation of epigenetic transcriptional control is a fundamental feature of cancer, particularly manifesting as increased promoter DNA methylation with associated aberrant gene silencing, which plays a significant role in tumor progression. We now globally map key chromatin parameters for genes with promoter CpG island DNA hypermethylation in colon cancer cells by combining microarray gene expression analyses with chromatin immunoprecipitation-on-chip technology. We first show that the silent state of such genes universally correlates with a broad distribution of a low but distinct level of the PcG-mediated histone modification, methylation of lysine 27 of histone 3 (H3K27me), and a very low level of the active mark H3K4me2. This chromatin pattern, and particularly H3K4me2 levels, crisply separates DNA-hypermethylated genes from those where histone deacetylation is responsible for transcriptional silencing. Moreover, the chromatin pattern can markedly enhance identification of truly silent and DNA-hypermethylated genes. We additionally find that when DNA-hypermethylated genes are demethylated and reexpressed, they adopt a bivalent chromatin pattern, which is associated with the poised gene expression state of a large group of embryonic stem cell genes and is characterized by an increase in levels of both the H3K27me3 and H3K4me2 marks. Our data have great relevance for the increasing interest in reexpression of DNA-hypermethylated genes for the treatment of cancer.
Facial port wine stains in childhood: prediction of the rate of improvement as a function of the age of the patient, size and location of the port wine stain and the number of treatments with the pulsed dye (585 nm) laser
Authors: None Nguyen, None Yohn, None Huff, None Weston, None Morelli
Journal: British Journal of Dermatology (1998)

In this study we examined the rate of decrease in size of facial port wine stains (PWS) as a function of number of treatments, lesion size, lesion location and patients' age. This study was performed at the University of Colorado Hospital Outpatient Dermatology Center, Denver, U.S.A. A consecutive sample of 91 patients 18 years of age or younger with facial PWS in which the entire lesion was treated at each visit were studied. Included were all patients who had a minimum of five treatments or complete clearance of their lesion in fewer than five treatments. Patients were evaluated following one, five and 10 treatments with the pulsed (450 s) dye (585 nm) laser. Improvement was defined as the percentage decrease in the size of the PWS. For all patients, the first five treatments resulted in a mean decrease in size of 55% while the second five treatments (38 patients) only improved the mean decrease in size by 18%. Grouped by location, the mean decreases in size from the first five and the second five treatments were as follows: central forehead = 100%, 0%; peripheral face = 58%, 28%; central face = 48%, 14%; and mixed (combination of peripheral and central face) = 21%, 9%. All central forehead PWS completely cleared within five treatments while none of the mixed PWS did so even with an average of 14 treatments. Grouped by size, mean decrease in size was highest for small lesions: < 20 cm2 = 67%, 21%; 20 to < 40 cm2 = 45%, 8%; and > 40 cm2 = 23%, 29%. Grouped by age, mean decrease in size was highest for young children: < 1-year-old = 63%, 33%; 1 to < 6 years = 48%, 15%; and older than 6 years = 54%, 10%. For all patients studied, maximal improvement was obtained in the first five treatments. Major determinants of treatment response in order of decreasing importance are PWS location, size and patients' age. The most successful responses are seen in young patients (less than 1 year old) with small PWS (under 20 cm2) that are located over bony areas of the face such as the central forehead. These three determinants may be useful tools to guide patient expectations and to predict the rate of improvement of PWS to pulsed dye laser treatment.
Selenium Suppresses Leukemia through the Action of Endogenous Eicosanoids
Authors: Ujjawal H. Gandhi, Naveen Kaushal, Shailaja Hegde, Emily R. Finch, Avinash K. Kudva, Mary J. Kennett, Craig T. Jordan, Robert F. Paulson, K. Sandeep Prabhu
Journal: Cancer Research (2014)

Abstract Eradicating cancer stem-like cells (CSC) may be essential to fully eradicate cancer. Metabolic changes in CSC could hold a key to their targeting. Here, we report that the dietary micronutrient selenium can trigger apoptosis of CSC derived from chronic or acute myelogenous leukemias when administered at supraphysiologic but nontoxic doses. In leukemia CSC, selenium treatment activated ATM-p53–dependent apoptosis accompanied by increased intracellular levels of reactive oxygen species. Importantly, the same treatment did not trigger apoptosis in hematopoietic stem cells. Serial transplantation studies with BCR–ABL-expressing CSC revealed that the selenium status in mice was a key determinant of CSC survival. Selenium action relied upon the endogenous production of the cyclooxygenase-derived prostaglandins Δ12-PGJ2 and 15d-PGJ2. Accordingly, nonsteroidal anti-inflammatory drugs and NADPH oxidase inhibitors abrogated the ability of selenium to trigger apoptosis in leukemia CSC. Our results reveal how selenium-dependent modulation of arachidonic acid metabolism can be directed to trigger apoptosis of primary human and murine CSC in leukemia. Cancer Res; 74(14); 3890–901. ©2014 AACR.
Central Nervous System Atypical Teratoid/Rhabdoid Tumor: Results of Therapy in Children Enrolled in a Registry
Authors: Joanne M. Hilden, Sharon Meerbaum, Peter Burger, Jonathan Finlay, Anna Janss, Bernd W. Scheithauer, Andrew W. Walter, Lucy B. Rorke, Jaclyn A. Biegel
Journal: Journal of Clinical Oncology (2004)

Atypical teratoid/rhabdoid tumor (AT/RT) of the CNS is an extremely rare and aggressive tumor of early childhood. The poor outcome with conventional infant brain tumor therapy has resulted in a lack of clear treatment guidelines. A registry has been established to create an outcomes database and to facilitate biology studies for this tumor.A standardized data sheet was provided to treating physicians listing the reports that were to be sent to the registry for abstraction. Follow-up information was sought twice yearly.Information was complete for 42 patients. Median age at diagnosis was 24 months. Nine patients (21%) had disseminated disease at diagnosis. Sixteen tumors were infratentorial; 26 were supratentorial. Twenty patients (48%) received a primary complete resection. Primary therapy included chemotherapy in all patients, radiotherapy in 13 patients (31%), stem-cell rescue in 13 patients (31%), and intrathecal chemotherapy in 16 patients (38%). Recurrent or progressive disease was reported in nine and 19 patients, respectively. Twenty-seven patients (64%) are dead of disease (3 to 62 months from diagnosis) and one patient died of toxicity. Fourteen patients (33%) show no evidence of disease (9.5 to 96 months from diagnosis). The median survival is 16.75 months and the median event-free survival is 10 months.Aggressive therapy has prolonged the natural history in a subset of children. Prospective multi-institutional and national clinical trials designed specifically for AT/RT are needed. Enrollment onto the AT/RT registry should be continued.
Classification of neurological abnormalities in children with congenital melanocytic naevus syndrome identifies magnetic resonance imaging as the best predictor of clinical outcome
Authors: R. Waelchli, S.E. Aylett, D. Atherton, D.J. Thompson, W.K. Chong, V.A. Kinsler
Journal: British Journal of Dermatology (2015)

The spectrum of central nervous system (CNS) abnormalities described in association with congenital melanocytic naevi (CMN) includes congenital, acquired, melanotic and nonmelanotic pathology. Historically, symptomatic CNS abnormalities were considered to carry a poor prognosis, although studies from large centres have suggested a much wider variation in outcome.To establish whether routine MRI of the CNS is a clinically relevant investigation in children with multiple CMN (more than one at birth), and to subclassify radiological abnormalities.Of 376 patients seen between 1991 and 2013, 289 fulfilled our criterion for a single screening CNS MRI, which since 2008 has been more than one CMN at birth, independent of size and site of the largest naevus. Cutaneous phenotyping and radiological variables were combined in a multiple regression model of long-term outcome measures (abnormal neurodevelopment, seizures, requirement for neurosurgery).Twenty-one per cent of children with multiple CMN had an abnormal MRI. Abnormal MRI was the most significant predictor of all outcome measures. Abnormalities were subclassified into group 1 'intraparenchymal melanosis alone' (n = 28) and group 2 'all other pathology' (n = 18). Group 1 was not associated with malignancy or death during the study period, even when symptomatic with seizures or developmental delay, whereas group 2 showed a much more complex picture, requiring individual assessment.For screening for congenital neurological lesions a single MRI in multiple CMN is a clinically relevant strategy. Any child with a stepwise change in neurological/developmental symptoms or signs should have an MRI with contrast of the brain and spine to look for new CNS melanoma.
Maternal Nrf2 and gluthathione-S-transferase polymorphisms do not modify associations of prenatal tobacco smoke exposure with asthma and lung function in school-aged children
Authors: A. J. Henderson, R. B. Newson, M. Rose-Zerilli, S. M. Ring, J. W. Holloway, S. O. Shaheen
Journal: Thorax (2010)

<h3>Abstract</h3> <h3>Background</h3> The transition from controlled to compulsive drug use occurs in a small proportion of individuals characterizing substance use disorder (SUD). The "3-Criteria" model developed on the operationalization of key DSM diagnostic criteria of SUD has helped to shed light on behavioural and biological factors involved in these divergent trajectories. However, the classification strategy on which the model has hitherto relied puts as much weight on the cohort to which the individual belongs as on their own characteristics, thereby limiting its construct validity with regards to the individual-based diagnostic approach in humans. <h3>Methods</h3> Large datasets resulting from the combination of behavioral data from several of our previous studies on addiction-like behavior for cocaine or alcohol were fed to a variety of machine learning algorithms (each consisting of an unsupervised clustering method combined with a supervised machine learning algorithm) in order to develop a classifier that identifies resilient and vulnerable rats with high precision and reproducibility irrespective of the cohort to which they belong. <h3>Results</h3> A classifier based on K-median or K-mean clustering (for cocaine or alcohol, respectively) followed by Artificial Neural Networks emerged as the best tool reliably and accurately to predict if a single rat is vulnerable or resilient to addiction as operationalized in the 3-Criteria model. Thus, all the rats previously characterized as 0 or 3crit in individual cohorts were correctly labelled as Resilient or Vulnerable, respectively, by this classifier. <h3>Conclusion</h3> The present machine learning-based classifier objectively labels single individuals as resilient or vulnerable to develop addiction-like behaviour in multisymptomatic preclinical models of cocaine or alcohol addiction in rats, thereby increasing their heuristic value with regards to the human situation.
Generalizability of Trial Results to Elderly Medicare Patients With Advanced Solid Tumors (Alliance 70802)
Authors: Elizabeth B. Lamont, Richard L. Schilsky, Yulei He, Hyman Muss, Harvey Jay Cohen, Arti Hurria, Ashley Meilleur, Hedy L. Kindler, Alan Venook, Rogerio Lilenbaum, Harvey Niell, Richard M. Goldberg, Steven Joffe
Journal: JNCI Journal of the National Cancer Institute (2014)

In the United States, patients who enroll in chemotherapy trials seldom reflect the attributes of the general population with cancer, as they are often younger, more functional, and have less comorbidity. We compared survival following three chemotherapy regimens according to the setting in which care was delivered (ie, clinical trial vs usual care) to determine the generalizability of clinical trial results to unselected elderly Medicare patients.Using SEER-Medicare data, we estimated survival for elderly patients (ie, age 65 years or older, n = 14097) with advanced pancreatic or lung cancer following receipt of one of three guideline-recommended first-line chemotherapy regimens. We compared their survival to that of similarly treated clinical trial enrollees, without age restrictions, with the same diagnosis and stage (n = 937). All statistical tests were two-sided.Trial patients were 9.5 years younger than elderly Medicare patients. Medicare patients were more often white and tended to live in areas of greater educational attainment than trial enrollees. For each tumor type, Medicare patients who were 75 years or older had median survivals that were six to eight weeks shorter than those of trial patients (4.3 vs 5.8 months following treatment with single agent gemcitabine for advanced pancreatic cancer, P = .03; 7.3 vs 8.9 months following treatment with carboplatin and paclitaxel for stage IV non-small cell lung cancer, P = .91; 8.2 vs 10.2 months following treatment with CDDP/ VP16 for extensive stage small cell lung cancer, P ≤ .01), whereas younger Medicare patients had survival times that were similar to those of trial patients.Results of clinical trials for advanced pancreatic cancer and lung cancers tended to correctly estimate survival for Medicare patients aged 65 to 74 years, but to overestimate survival for older Medicare patients by six to eight weeks. These estimates of Medicare patients' survival may aid subsequent patients and their oncologists in treatment decision-making.
Gut Microbiota Metabolites of Dietary Lignans and Risk of Type 2 Diabetes: A Prospective Investigation in Two Cohorts of U.S. Women
Authors: Qi Sun, Nicole M. Wedick, An Pan, Mary K. Townsend, Aedin Cassidy, Adrian A. Franke, Eric B. Rimm, Frank B. Hu, Rob M. van Dam
Journal: Diabetes Care (2014)

To examine urinary levels of enterolactone and enterodiol, intestinal microbial metabolites of dietary lignans, in relation to type 2 diabetes (T2D) risk.Urinary concentrations of the lignan metabolites were assayed by liquid chromatography-mass spectrometry among 1,107 T2D and 1,107 control subjects in a nested case-control study conducted in participants from the Nurses' Health Study (NHS) and NHSII. Subjects were free of diabetes, cardiovascular disease, and cancer at urine sample collection in 1995-2001. Incident self-reported T2D cases identified through 2008 were confirmed with a validated questionnaire.In both cohorts, T2D subjects had significantly lower concentrations of both enterolactone and enterodiol than control subjects. After multivariate adjustment for lifestyle and dietary risk factors of T2D, urinary concentrations of enterolactone were significantly associated with a lower risk of T2D (pooled odds ratio [OR] comparing the extreme quartiles 0.62 [95% CI 0.44, 0.88], P for trend = 0.003). Higher urinary concentrations of enterodiol were also marginally significantly associated with a lower T2D risk (pooled OR comparing extreme quartiles 0.67 [95% CI 0.48, 0.96], P for trend = 0.08). When concentrations of both metabolites were combined to reflect total lignan intake, the OR was 0.70 (95% CI 0.53, 0.92) for each SD increment of total lignan metabolites.These results indicate that lignan metabolites, especially enterolactone, are associated with a lower risk of T2D in U.S. women. Further studies are needed to replicate these findings and to explore potential mechanisms underlying the observed association.
Echocardiographic abnormalities in ankylosing spondylitis.
Authors: T W O'Neill, G King, I M Graham, J Molony, B Bresnihan
Journal: Annals of the Rheumatic Diseases (1992)

Twenty four patients with ankylosing spondylitis of 10 or more years9 duration were assessed for evidence of cardiac disease. Seven patients (29%) had evidence of cardiac disease, including one patient with a pericardial effusion, three with conduction abnormalities, and two with aortic incompetence. Aortic incompetence in one patient was clinically silent and was detected only with Doppler echocardiography. This patient had, in addition, thickening of the posterior aortic wall, an echocardiographic feature not previously described in ankylosing spondylitis. There was no evidence of aortic valve disease in a control group matched for age and sex. Patients with ankylosing spondylitis and cardiac abnormalities were older, had a longer disease duration, and more peripheral joint disease than those without cardiac abnormalities. Doppler echocardiography is a useful technique in the assessment of cardiac disease in ankylosing spondylitis and may detect aortic valve disease at an early preclinical stage.
Occult Hepatitis C Virus Infection among Hemodialysis Patients
Authors: Guillermina Barril, Inmaculada Castillo, María Dolores Arenas, Mario Espinosa, Juan Garcia-Valdecasas, Nuria Garcia-Fernández, Emilio González-Parra, José María Alcazar, Carmen Sánchez, José Carlos Diez-Baylón, Pilar Martinez, Javier Bartolomé, Vicente Carren[Combining Tilde]o
Journal: Journal of the American Society of Nephrology (2008)

Occult hepatitis C virus (HCV) infection (i.e., detectable HCV-RNA in the liver or peripheral blood mononuclear cells) in the absence of both serum HCV-RNA and anti-HCV antibodies has not been investigated in hemodialysis patients. In this study, real-time PCR and in situ hybridization was used to test for the presence of genomic and antigenomic HCV-RNA in peripheral blood mononuclear cells of 109 hemodialysis patients with abnormal levels of liver enzymes. Occult HCV infection, determined by the presence of genomic HCV-RNA, was found in 45% of the patients; 53% of these patients had ongoing HCV replication, indicated by the presence of antigenomic HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on hemodialysis and had significantly higher mean alanine aminotransferase levels during the 6 mo before study entry. Logistic regression analysis revealed that mortality was associated with age >60 yr (odds ratio 3.30; 95% confidence interval 1.05 to 10.33) and the presence of occult HCV infection (odds ratio 3.84; 95% confidence interval 1.29 to 11.43). In conclusion, the prevalence of occult HCV infection is high among hemodialysis patients with persistently abnormal values of liver enzymes of unknown cause. The clinical significance of occult HCV infection in these patients requires further study.
Optimal use of directional coronary atherectomy is required to ensure long-term angiographic benefit: A study with matched procedural outcome after atherectomy and angioplasty
Authors: Victor A.W.M. Umans, David Keane, David Foley, Eric Boersma, Rein Melkert, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (1994)