tbuckley/cabot-search huggingface dataset:
Prognostic Impact of Morphologic and Phenotypic Features of Childhood ALK-Positive Anaplastic Large-Cell Lymphoma: Results of the ALCL99 Study
Authors: Laurence Lamant, Keith McCarthy, Emanuele d'Amore, Wolfram Klapper, Atsuko Nakagawa, Maximo Fraga, Jadwiga Maldyk, Ingrid Simonitsch-Klupp, Ilske Oschlies, Georges Delsol, Audrey Mauguen, Laurence Brugières, Marie-Cécile Le Deley
Journal: Journal of Clinical Oncology (2011)

The prognostic value of pathologic characteristics of childhood ALK-positive anaplastic large-cell lymphomas (ALCL), such as histologic subtypes, immunophenotype, and presence of the t(2;5) translocation or its variants, was assessed.All 375 patients with systemic ALK-positive ALCL included in an international trial launched by the European Intergroup for Childhood Non-Hodgkin's Lymphoma were reviewed by an international panel of pathologists based on conventional hematoxylin and eosin-stained and immunostained sections and classified according to the 2001 WHO classification.A small-cell (SC) or lymphohistiocytic (LH) component was observed in 114 (32%) of 361 patients, whereas ALCL of common type was diagnosed in 235 (65%) of 361 patients. Regarding the histologic subtyping of patients within the two categories of ALCL (with v without SC/LH component), the concordance between the national and international reviews was quite good, with a κ index equal to 0.67 (95% CI, 0.57 to 0.75). The presence of an SC/LH component was significantly associated with a high risk of failure (hazard ratio [HR], 2.0; 95% CI, 1.3 to 3.0; P = .002) in the multivariate analysis controlling for clinical characteristics, as well as the perivascular pattern (HR, 1.7; 95% CI, 1.1 to 2.7; P = .01), whereas CD3 positivity was significantly associated with a high risk of failure only in univariate analysis.Our study, which to our knowledge includes the largest series of childhood systemic ALK-positive ALCL so far, demonstrates the adverse prognostic value of SC and/or LH morphologic features. Combining these histologic characteristics with other biologic or clinical factors might have a high potential for future risk stratification and treatment.
Recombinant Human Erythropoietins and Cancer Patients: Updated Meta-Analysis of 57 Studies Including 9353 Patients
Authors: Julia Bohlius, Jayne Wilson, Jerome Seidenfeld, Margaret Piper, Guido Schwarzer, Josie Sandercock, Sven Trelle, Olaf Weingart, Sue Bayliss, Benjamin Djulbegovic, Charles L. Bennett, Simon Langensiepen, Chris Hyde, Andreas Engert
Journal: JNCI Journal of the National Cancer Institute (2006)

This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events.
Thyroid Hormone Represses Protein Kinase C Isoform Expression and Activity in Rat Cardiac Myocytes
Authors: Vitalyi Rybin, Susan F. Steinberg
Journal: Circulation Research (1996)

We have previously demonstrated that at least four isoforms of protein kinase C (PKC; alpha, delta, epsilon, and zeta) are expressed in neonatal rat ventricular myocytes and that development is associated with a decline in their expression. The mechanism(s) regulating PKC isoform expression in ventricular myocytes is completely unknown. The developmental decline in PKC expression occurs, in large part, during the first 2 weeks of postnatal life, while thyroid hormone levels are known to be progressively increasing. Accordingly, this study examined the influence of thyroid hormone on PKC isoform expression to determine whether thyroid hormone can be implicated as a potential physiological regulator of PKC gene expression during normal cardiac development. Hypothyroidism was induced in adult rats by surgical thyroidectomy; thyroid status was manipulated in cultured neonatal ventricular myocytes by growth in serum-free medium with varying triiodothyronine (T3) levels. In each case, hypothyroidism was verified by a 10- to 50-fold increase in steady state mRNA for beta-myosin heavy chain. In hypothyroid adult ventricular myocardium, there was a selective 60% increase in the expression of PKC epsilon protein that corresponded to an increase in maximally stimulated PKC enzyme activity with PKC epsilon substrate peptide (epsilon pep) but not with histone as substrate. Northern blot analysis revealed a 70% increase in PKC epsilon mRNA, indicating that the regulatory effects of thyroid hormone are mediated, at least in part, at the message level. In neonatal ventricular myocytes, there was a T3-dependent reduction in immunoreactivity for both PKC alpha and PKC epsilon that was associated with significant reductions in both histone- and epsilon pep-kinase activities. The concentration of T3 that half-maximally repressed PKC alpha and PKC epsilon expression was approximately 0.5 nmol/L. Thyroid hormone had no effect on PKC delta and PKC zeta expression in neonatal or adult ventricular myocytes. PKC isoform expression in cardiac fibroblasts was not influenced by variations in the thyroid hormone concentration during culture. These results provide evidence that thyroid hormone specifically represses PKC alpha and PKC epsilon in the neonatal heart and PKC epsilon in the adult heart. Thyroid hormone-induced changes in PKC may play an important permissive role in the modulation of autonomic responsiveness in ventricular cardiomyocytes.
Posttranslational regulation of the NKG2D ligand Mult1 in response to cell stress
Authors: Timothy J. Nice, Laurent Coscoy, David H. Raulet
Journal: The Journal of Experimental Medicine (2009)

NKG2D is a major stimulatory receptor expressed by natural killer (NK) cells and some T cells. The receptor recognizes major histocompatability complex class I–like cell surface ligands that are poorly expressed by normal tissues but are often induced in transformed and infected cells. The existence of several NKG2D ligands in each individual, some with strikingly divergent protein sequences, raises the possibility that different ligands are regulated by distinct disease-associated stresses. The transcripts for some ligands, including murine UL16-binding proteinlike transcript 1 (Mult1), are abundant in certain normal tissues where cell surface expression is absent, suggesting the existence of translational or posttranslational regulation. We report here that under normal conditions, Mult1 protein undergoes ubiquitination dependent on lysines in its cytoplasmic tail and lysosomal degradation. Mult1 degradation and ubiquitination is reduced in response to stress imparted by heat shock or ultraviolet irradiation, but not by other forms of genotoxicity, providing a novel mechanism for stress-mediated cellular control of NKG2D ligand expression.
Brain Volume Findings in 6-Month-Old Infants at High Familial Risk for Autism
Authors: Heather Cody Hazlett, Hongbin Gu, Robert C. McKinstry, Dennis W.W. Shaw, Kelly N. Botteron, Stephen R. Dager, Martin Styner, Clement Vachet, Guido Gerig, Sarah J. Paterson, Robert T. Schultz, Annette M. Estes, Alan C. Evans, Joseph Piven
Journal: American Journal of Psychiatry (2012)

Objective: Individuals with autism as young as 2 years have been observed to have larger brains than healthy comparison subjects. Studies using head circumference suggest that brain enlargement is a postnatal event that occurs around the latter part of the first year. To the authors' knowledge, no previous brain imaging studies have systematically examined the period prior to age 2. In this study they used magnetic resonance imaging (MRI) to measure brain volume in 6-month-olds at high familial risk for autism. Method: The Infant Brain Imaging Study (IBIS) is a longitudinal imaging study of infants at high risk for autism. This cross-sectional analysis compared brain volumes at 6 months of age in high-risk infants (N=98) and infants without family members with autism (N=36). MRI scans were also examined for radiologic abnormalities Results: No group differences were observed for intracranial, cerebrum, cerebellum, or lateral ventricle volume or for head circumference. Conclusions: The authors did not observe significant group differences for head circumference, brain volume, or abnormalities in radiologic findings from a group of 6-month-old infants at high risk for autism. The authors are unable to conclude that these abnormalities are not present in infants who later go on to receive a diagnosis of autism; rather, abnormalities were not detected in a large group at high familial risk. Future longitudinal studies of the IBIS study group will examine whether brain volume differs in infants who go on to develop autism.
Cutaneous <i>Pneumocystis carinii</i> and <i>Cryptococcus neoformans</i> in AIDS
Authors: B. SANDLER, T. S. POTTER, K. HASHIMOTO
Journal: British Journal of Dermatology (1996)

A patient with AIDS was found to have skin lesions which contained the organisms Pneumocystis carinii and Cryptococcus neoformans. Both organisms were identified using haematoxylin and eosin, Gomori methenamine silver, Giemsa and mucicarmine stains. Electron microscopy was performed and confirmed their presence. The clinical presentation, histopathology, differential diagnosis and treatment of cutaneous P. carinii and C. neoformans in AIDS is presented.
Screening for Lung Cancer With Low-Dose Helical Computed Tomography: Anti-Lung Cancer Association Project
Authors: Tomotaka Sobue, Noriyuki Moriyama, Masahiro Kaneko, Masahiko Kusumoto, Toshiaki Kobayashi, Ryosuke Tsuchiya, Ryutaro Kakinuma, Hironobu Ohmatsu, Kanji Nagai, Hiroyuki Nishiyama, Eisuke Matsui, Kenji Eguchi
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Because efficacy of lung cancer screening using chest x-ray is controversial and insufficient, other screening modalities need to be developed. To provide data on screening performance of low-dose helical computed tomography (CT) scanning and its efficacy in terms of survival, a one-arm longitudinal screening project was conducted. PATIENTS AND METHODS: A total of 1,611 asymptomatic patients aged 40 to 79 years, 86% with smoking history, were screened by low-dose helical CT scan, chest x-ray, and 3-day pooled sputum cytology with a 6-month interval. RESULTS: At initial screening, the proportions of positive tests were 11.5%, 3.4%, and 0.8% with low-dose helical CT scan, chest x-ray, and sputum cytology, respectively. In 1,611 participants, 14 (0.87%) cases of lung cancer were detected, with 71% being stage IA disease and a mean tumor diameter of 19.8 mm. At repeated screening, the proportions of positive tests were 9.1%, 2.6%, and 0.7% with low-dose helical CT, chest x-ray, and sputum cytology, respectively. In 7,891 examinations, 22 (0.28%) cases of lung cancer were detected, with 82% being stage IA disease and a mean tumor diameter of 14.6 mm. The 5-year survival rate for screen-detected lung cancer was 76.2% and 64.9% for initial and repeated screening, respectively. CONCLUSION: Screening with low-dose helical CT has potential to improve screening efficacy in terms of reducing lung cancer mortality. An evaluation of efficacy using appropriate methods is urgently required.
Gastric mucosal hyperplasia via upregulation of gastrin induced by persistent activation of gastric innate immunity in major histocompatibility complex class II deficient mice
Authors: T Fukui
Journal: Gut (2005)

<b>Background and aim:</b> Major histocompatibility complex class II deficient (Aα<sup>0/0</sup>) mice have decreased CD4<sup>+</sup> T cells, making them immunologically similar to patients with acquired immunodeficiency syndrome (AIDS). Both patients with AIDS and Aα<sup>0/0</sup> mice have hypertrophic gastric folds. To clarify the mechanism of gastric mucosal hyperplasia, we investigated the pathophysiology and the role of the innate immunity in the stomach of Aα<sup>0/0</sup> mice. <b>Methods:</b> Stomachs from 1–6 month old Aα<sup>0/0</sup> mice, kept under specific pathogen free conditions, were examined at 1 month intervals histologically and immunohistochemically. Gene expression of proinflammatory cytokines, Toll-like receptors (TLRs), cyclooxygenase (COX)-2, and myeloperoxidase (MPO) activity in the gastric mucosa was investigated. Serum gastrin levels and gastric acidity were measured. Bacterial culture of the stomach was performed. To clarify the roles of hypergastrinaemia in the gastric mucosa, a gastrin receptor antagonist (AG041R) was administered. <b>Results:</b> Aα<sup>0/0</sup> mice had a diffusely thick corpus mucosa with infiltration of CD11b<sup>+</sup> granulocytes and macrophages. Anti-Ki67 staining demonstrated expansion of the proliferating neck zone. Gene expression of interleukin 1β, interferon γ, TLR-2, TLR-4, and COX-2 were upregulated, and MPO activity was increased. Only a small amount of non-pathogenic bacteria was detected in the stomach. Serum gastrin levels and Reg-Iα positive cells in the gastric mucosa increased, despite normal gastric acidity. After treatment with AG041R, gastric mucosal thickness was significantly reduced. <b>Conclusion:</b> Persistent activation of innate immunity in the stomach induced gastric mucosal hyperplasia through upregulation of gastrin synthesis in Aα<sup>0/0</sup> mice, suggesting a pathophysiology similar to the gastric changes in patients with AIDS.
Maximizing the Utilization of Donor Organs Offered for Lung Transplantation
Authors: ELI GABBAY, TREVOR J. WILLIAMS, ANNE P. GRIFFITHS, LOUISE M. MACFARLANE, TOM C. KOTSIMBOS, DONALD S. ESMORE, GREGORY I. SNELL
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The number of patients awaiting lung transplantation (LT) and waiting time for surgery is increasing. In Australia, LT rates are 4. 6/million population/yr, which despite low organ donation rates, are the highest published in the world. The Australian organ allocation system allows identification of marginal donors and therapeutic manipulation where appropriate. This study aims to assess the impact of utilization of marginal donors and aggressive donor management. A comparison between published donor criteria and local practice is made, allowing assessment of the effect of using marginal donors on outcome. Donor management included antibiotic therapy, strict fluid management, physiotherapy, bronchoscopy and bronchial toilet, and alteration of ventilatory settings including initiation of pressure support. Blood gases were repeated to assess the results of interventions. Between January 1, 1995 and May 31, 1998, we performed 140 transplants from 112 of 219 (51%) lung donor offers. Of these donors, 48 (43%) satisfied all published criteria for suitable donor organs (Group 1 = ideal donors) and 64 (57%) did not (Group 2 = marginal donors). Criteria breached by the marginal donors were: an initial ratio of arterial oxygen pressure to fraction of inspired oxygen (PaO2/FIO2) < 300 mm Hg (n = 20), abnormal radiology (n = 39), pulmonary infection (n = 24), 20 pack-years smoking (n = 5) and age > 55 yr (n = 4). Therapeutic manipulation resulted in improvement in the PaO2/FIO2 ratio in 20 donors (Group 3) who would not otherwise have been used. Immediate and 24 h postoperative gas exchange and length of intensive care unit (ICU) stay was not different for recipients from donors from all three groups. Overall survival was 94% at 30 d, 83% at 1 yr, 70% at 2 yr, and 62% at 3 yr and was not significantly different from the three groups. We conclude that organ utilization can be maximized by therapeutic manipulation and utilization of marginal donors without compromising results from transplantation.
Reduced Nasal Nitric Oxide in Diffuse Panbronchiolitis
Authors: HITOSHI NAKANO, HIROSHI IDE, MASANOBU IMADA, SHINOBU OSANAI, TORU TAKAHASHI, KENJIROU KIKUCHI, JUN IWAMOTO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Diffuse panbronchiolitis (DPB) is a pulmonary disease of unknown origin with inflammation in the respiratory bronchioles, bronchiectasis, and recurrent sinusitis. Patients with DPB suffer from chronic airway infections resulting from mucociliary dysfunction. Whereas a high concentration of nasal nitric oxide (NO) has been documented in healthy subjects, only two diseases are known to reduce nasal NO: primary ciliary dyskinesia syndrome and cystic fibrosis. We hypothesized that patients with DPB have abnormal levels of nasal NO. To test our hypothesis, we measured NO with the chemiluminescence technique. Air was sampled directly from the nose in 15 healthy subjects and eight patients with DPB. Nasal NO was 88% lower in DPB patients than in the age-matched control subjects (69 ± 70 versus 556 ± 87 nl/min; p < 0.001). Treatment with erythromycin for 2 wk did not alter the nasal NO in four control subjects. DPB is the third pulmonary disease in which nasal NO is low. The reduced nasal NO may well be involved in the pathogenesis of DPB, and NO measurements may serve as a noninvasive test in the diagnosis of DPB.
Abdominal Subcutaneous Adipose Tissue: A Protective Fat Depot?
Authors: Stacy A. Porter, Joseph M. Massaro, Udo Hoffmann, Ramachandran S. Vasan, Christopher J. O'Donnel, Caroline S. Fox
Journal: Diabetes Care (2009)

Obesity is associated with increased metabolic and cardiovascular risk. The ectopic fat hypothesis suggests that subcutaneous fat may be protective, but this theory has yet to be fully explored.Participants from the Framingham Heart Study (n = 3,001, 48.5% women) were stratified by visceral adipose tissue (VAT) into sex-specific tertiles. Within these tertiles, age-adjusted abdominal subcutaneous adipose tissue (SAT) tertiles were examined in relation to cardiometabolic risk factors.In the lowest VAT tertile, risk factor prevalence was low, although systolic blood pressure in women and rates of high triglycerides, impaired fasting glucose, hypertension, and the metabolic syndrome in men increased with increasing SAT tertile (all P < 0.04). In contrast, in the top VAT tertile, lower triglycerides were observed in men with increasing SAT (64.4% high triglycerides in SAT tertile 1 vs. 52.7% in SAT tertile 3, P = 0.03). Similar observations were made for women, although results were not statistically significant (50.6% high triglycerides in SAT tertile 1 vs. 41.0% in tertile 3, P = 0.10). Results in the highest VAT tertile were notable for a lack of increase in the prevalence of low HDL in men and women and in rates of impaired fasting glucose in men with increasing subcutaneous fat, despite sizable differences in BMI across SAT tertiles (27.1 to 36.3 kg/m(2)[women]; 28.1 to 35.7 kg/m(2)[men]).Although adiposity increases the absolute risk of metabolic and cardiovascular disease, abdominal subcutaneous fat is not associated with a linear increase in the prevalence of all risk factors among the obese, most notably, high triglycerides.
CD26 expression in donor stem cell harvest and its correlation with engraftment in human haematopoietic stem cell transplantation: potential predictor of early engraftment
Authors: K Prabhash, N Khattry, A Bakshi, R Karandikar, A Joshi, S Kannan, P S R K Sastry, P Parikh, J A Kode
Journal: Annals of Oncology (2009)
Depigmented hypertrichosis following Blaschko’s lines associated with cerebral and ocular malformations: a new neurocutaneous, autosomal lethal gene syndrome from the group of epidermal naevus syndromes?
Authors: S. Schauder, F. Hanefeld, U.M. Noske, B. Zoll
Journal: British Journal of Dermatology (2000)

Abstract The lines of Blaschko represent one of the cutaneous patterns of mosaicism followed by various skin disorders. Developmental abnormalities affecting other tissues derived from the embryonic ectoderm and mesoderm are occasionally associated. We describe a 30-year-old man with depigmented, bilateral hypertrichosis and dilated follicular orifices following Blaschko’s lines associated with cerebral and ocular malformations. The findings suggest a previously unreported neurocutaneous, autosomal lethal gene syndrome from the group of epidermal naevus syndromes.
Virological and serological aspects of hepatitis B and the delta agent.
Authors: G Hess
Journal: Gut (1993)

The hepatitis B virus (HBV) belongs to a group of viruses termed hepadnaviruses. The 3.2 kb genome encodes for a variety of proteins involved in viral replication (p-gene), transactivation (x-gene), or encodes for structural proteins (c- and s-genes). Several viral and non-viral functions determine the clinical course of HBV infection. The hepatitis D virus resembles a viroid and requires the HBV as a helper virus. The interaction between the viruses is not well understood. More information on the interaction between the human host and viruses is needed to help improve the treatment.
MYC Is Activated by USP2a-Mediated Modulation of MicroRNAs in Prostate Cancer
Authors: Barbara Benassi, Richard Flavin, Luigi Marchionni, Silvio Zanata, Yunfeng Pan, Dipanjan Chowdhury, Marina Marani, Sabrina Strano, Paola Muti, Giovanni Blandino, Massimo Loda
Journal: Cancer Discovery (2012)

Ubiquitin-specific protease 2a (USP2a) is overexpressed in almost half of human prostate cancers and c-Myc is amplified in one third of these tumor types. Transgenic MYC expression drives invasive adenocarcinomas in the murine prostate. We show that overexpression of USP2a downregulates a set of microRNAs that collectively increase MYC levels by MDM2 deubiquitination and subsequent p53 inactivation. By establishing MYC as a target of miR-34b/c, we demonstrate that this cluster functions as a tumor suppressor in prostate cancer cells. We identify a distinct mRNA signature that is enriched for MYC-regulated transcripts and transcription factor binding sites in USP2a overexpressing prostate cancer cells. We demonstrate that these genes are associated with an invasive phenotype in human prostate cancer and that the proliferative and invasive properties of USP2a overexpressing cells are MYC-dependent. These results highlight an unrecognized mechanism of MYC regulation in prostate cancer and suggest alternative therapeutic strategies in targeting MYC.The deubiquitinating enzyme USP2a has previously been shown to be oncogenic, overexpressed in almost half of human prostate adenocarcinomas, and prolongs the half-life of targets such as fatty acid synthase, MDM2, and cyclin D1. Here, we highlight a new mechanism by which USP2a enhances MYC levels through the modulation of specific subsets of microRNAs in prostate cancer, suggesting alternative therapeutic strategies for targeting MYC.
Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling
Authors: P. K. Epling-Burnette, Lubomir Sokol, Xianhong Chen, Fanqi Bai, Junmin Zhou, Michelle A. Blaskovich, JianXiang Zou, Jeffrey S. Painter, Todd D. Edwards, Lynn Moscinski, Jeffrey A. Yoder, Julie Y. Djeu, Said Sebti, Thomas P. Loughran, Sheng Wei
Journal: Blood (2008)