tbuckley/cabot-search huggingface dataset:
Analysis of Platelets From Patients With Thrombocythemia for Reverse Transcriptase and Virus-Like Particles2
Authors: Isadore Brodsky, Anthony A. Fuscaldo, Barry J. Erlick, Elizabeth W. Kingsbury, Gretchen M. Schultz, Kathryn E. Fuscaldo
Journal: JNCI Journal of the National Cancer Institute (1975)

A preliminary analysis of an RNA-directed DNA polymerase was made and a C-type virus-like particle was identified in platelets from 2 patients with the myeloproliferative disorder thrombocythemia (primary; essential, hemorrhagic, or idiopathic thrombocythemia). Platelet homogenates were centrifuged through a sucrose equilibrium density gradient. Both endogenous and exogenous DNA polymerase activity was found at a density of 1.19 g/ml. No activity was seen at comparable densities in control gradients. Electron micrographs of thin sections of these platelets revealed a particle with the morphologic characteristics of a C-type virus; however, the diameter of this particle was about 80 nm, slightly lower than that commonly found for C-type particles. Critical-point dried specimens, from the fractions of the sucrose gradient at which DNA polymerase activity was found, contained particles of the same size and morphology as those in the thin sections.
The Neuronal Pentraxin-2 Pathway Is an Unrecognized Target in Human Neuroblastoma, Which Also Offers Prognostic Value in Patients
Authors: Alice Bartolini, Daniela Di Paolo, Alessio Noghero, Daniele Murgia, Angela R. Sementa, Michele Cilli, Renata Pasqualini, Wadih Arap, Federico Bussolino, Mirco Ponzoni, Fabio Pastorino, Serena Marchiò
Journal: Cancer Research (2015)

Neuronal pentraxins (NPTX) and their corresponding receptors (NPTXR) have been studied as synapse-associated proteins in the nervous system, but their role in cancer is largely unknown. By applying a multidisciplinary, high-throughput proteomic approach, we have recently identified a peptide ligand motif for targeted drug delivery to neuroblastoma. Here, we report the sequence similarity between this peptide and a conserved portion of the pentraxin domain that is involved in the homo- and hetero-oligomerization of NPTX2 and NPTXR. We show that, in comparison with normal tissues, NPTX2 and NPTXR are overexpressed in vivo in mouse models, as well as in human Schwannian stroma-poor, stage IV neuroblastoma. Both proteins are concentrated in the vicinity of tumor blood vessels, with NPTXR also present on neuroblastic tumor cells. In vivo targeting of NPTX2 and NPTXR with the selected peptide or with specific antibodies reduces tumor burden in orthotopic mouse models of human neuroblastoma. In vitro interference with this ligand/receptor system inhibits the organization of neuroblastoma cells in tumor-like masses in close contact with vascular cells, as well as their adhesion to normal microenvironment-derived cells, suggesting a role in the cross-talk between tumor and normal cells in the early steps of neuroblastoma development. Finally, we show that NPTX2 is a marker of poor prognosis for neuroblastoma patients.
Cellular and molecular mechanisms of cyclosporin nephrotoxicity.
Authors: J B Kopp, P E Klotman
Journal: Journal of the American Society of Nephrology (1990)

Cyclosporin therapy is associated with several forms of nephrotoxicity, the most significant of which are reversible impairment of glomerular filtration and irreversible interstitial fibrosis. Impaired glomerular filtration is due to both reduction in Kf, the glomerular capillary ultrafiltration coefficient, and to reduction in renal blood flow. The mechanisms responsible for the low Kf are not well defined, but heightened mesangial cell contractility may contribute. Reduced renal blood flow with chronic cyclosporin therapy arises from both endothelial damage and altered eicosanoid metabolism, in particular increased thromboxane synthesis. Renal interstitial fibrosis, which develops in some patients after approximately 6-12 months of cyclosporin therapy, poses a major limitation to the chronic use of the drug. Two mechanisms likely contribute to cyclosporin-associated interstitial fibrosis. First, endothelial injury and vasoconstriction produce renal ischemia, which in turn is associated with enhanced synthesis of extracellular matrix proteins. Second, cyclosporin likely influences the accumulation of matrix proteins in the renal interstitium through nonhemodynamic mechanisms, as suggested by altered matrix accumulation in non-renal tissues. This effect of cyclosporin may be direct or indirect, via mediators including cytokines, peptide growth factors, and thromboxane. The molecular mechanisms of cyclosporin action on immunologic and mesenchymal cells are active areas of investigation. Intracellular targets of cyclosporin include mitochondrial respiration, cellular calcium signaling, protein kinase C, protein synthesis, and peptidyl-prolyl isomerases. However, the significance of these intracellular effects for cyclosporin nephrotoxicity remains to be demonstrated.
A randomized, open-label phase II study of efatutazone in combination with FOLFIRI as second-line therapy for metastatic colorectal cancer (mCRC).
Authors: John Marshall, Dale Edward Shuster, Terri Robin Goldberg, Catherine Copigneaux, Shuquan Chen, Hamim Zahir, Dipen Dutta, Mansoor N. Saleh, Michael J. Pishvaian, Mirta Susana Varela, Felipe Palazzo, Nicolas Lazaretti, Cassia Costa, Eugenia Loredo, Jorge Leon, Reinhard W. Von Roemeling
Journal: Journal of Clinical Oncology (2014)

535^ Background: Efatutazone, a highly-selective peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has shown efficacy and manageable toxicity in phase I trials in solid tumors, including CRC. This study evaluated efatutazone in combination with chemotherapy for second-line mCRC. Methods: Patients (pts) from the United States and Latin America with mCRC progressing after first-line therapy not containing irinotecan were stratified by Eastern Cooperative Oncology Group (ECOG) status (0/1 vs. 2) and randomized 1:1 to efatutazone + FOLFIRI (E+F) or FOLFIRI alone (F). Treatment was administered in 4-week cycles until disease progression (PD), unacceptable toxicity, or consent withdrawal. Efatutazone (0.5 mg) was administered orally, twice daily; FOLFIRI (irinotecan 180 mg/m 2 , leucovorin 400 mg/m 2 , 5-fluorouracil 1200 mg/m 2 /d x 2 days) was administered intravenously once every 2 weeks immediately after efatutazone. The primary end point, progression-free survival (PFS) rate at week 16, was assessed locally according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.0. Results: Characteristics of the 100 randomized pts were generally well balanced between the E+F and F treatment arms: median age, 59.7 vs. 58.3 years; male, 56% vs 56%; and ECOG 0/1, 98% vs. 92%. Across the arms, more pts discontinued due to PD than toxicity: 49% vs. 19%, respectively. While PFS rate at week 16 was 60% vs. 67% for the E+F vs F arms (p = 0.30), overall, PFS was somewhat longer with E+F than with F (hazard ratio [HR], 0.87; 90% [confidence interval [CI], 0.57–1.32) with medians of 4.4 vs. 4.2 months, respectively. The objective response rate also favored E+F over F (20% vs. 14%). Overall survival was not significantly different (HR, 0.95; 90% CI, 0.65–1.38). Fluid retention, which was managed with diuretics, was more frequent with E+F than with F: 86% vs. 12% (grade 3/4: 12% vs. 0%). Hematologic adverse events, including neutropenia (66% vs. 20%; grade 3/4: 44% vs. 12%) and febrile neutropenia (14% vs 0%), were more common with E+F than with F. Conclusions: Efatutazone minimally improved efficacy of FOLFIRI for CRC and increased neutropenia and fluid retention. Clinical trial information: NCT00967616.
Isotopic immunoglobulin: a new systemic therapy for advanced Hodgkin's disease.
Authors: R E Lenhard, S E Order, J J Spunberg, S O Asbell, S A Leibel
Journal: Journal of Clinical Oncology (1985)

Thirty-eight patients with advanced, progressive Hodgkin's disease who had relapsed from or who had not responded to treatment with at least two potentially curative combination chemotherapy regimens were entered into this phase 2 study. All patients received 131I antiferritin antibody administered intravenously (IV) at a dose of 30 mCi on day 0 and 20 mCi on day 5. Antibody was derived from rabbit, pig, and monkey species. Objective partial remission of measurable disease was recorded in 40% of patients. Symptomatic response was recorded in 77% of patients. Toxicity was restricted to bone marrow depression with thrombocytopenia greater than leukopenia. These responses are comparable to other reported phase 2 drugs in this patient population and subsequent trials of antibody free of radioactivity and antibody using a beta emitting isotope are being carried out to expand upon these results.
Lactobacillus salivarius plus fructo-oligosaccharide is superior to fructo-oligosaccharide alone for treating children with moderate to severe atopic dermatitis: a double-blind, randomized, clinical trial of efficacy and safety
Authors: K.-G. Wu, T.-H. Li, H.-J. Peng
Journal: British Journal of Dermatology (2011)

Journal Article Lactobacillus salivarius plus fructo‐oligosaccharide is superior to fructo‐oligosaccharide alone for treating children with moderate to severe atopic dermatitis: a double‐blind, randomized, clinical trial of efficacy and safety Get access K.‐G. Wu, K.‐G. Wu Departments of Pediatrics Keh‐Gong Wu. E‐mail: kgwu@vghtpe.gov.tw Search for other works by this author on: Oxford Academic Google Scholar T.‐H. Li, T.‐H. Li Departments of PediatricsDepartment of Pediatrics, Hualien Armed Forces General Hospital, Hualien, Taiwan Search for other works by this author on: Oxford Academic Google Scholar H.‐J. Peng H.‐J. Peng Medical Research and Education, Taipei Veterans General Hospital and National Yang‐Ming University, No. 201, Sec. 2, Shih‐Pai Road, Taipei 112, Taiwan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 1, 1 January 2012, Pages 129–136, https://doi.org/10.1111/j.1365-2133.2011.10596.x Published: 01 January 2012 Article history Accepted: 22 August 2011 Published: 01 January 2012
Low frequency of resistant pathogens in nursing home acquired pneumonia: A prospective study and systematic review
Authors: Catriona Rother, Waleed Salih, Aran Singanayagam, James D. Chalmers
Journal: European Respiratory Journal (2013)

Introduction  It has been suggested that nursing home acquired pneumonia (NHAP) should be managed differently to community-acquired pneumonia (CAP) due to a higher frequency of potentially resistant pathogens.  Methods  This study describes two analyses: first, a prospective observational study of 1883 patients with CAP was used to compare microbiology between NHAP and CAP patients. Patients were classified as NHAP or CAP based on admission residency status. In the second analysis, a systematic review and meta-analysis compared the microbiology and outcomes of NHAP compared to CAP from all published comparative studies. Methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and enterobactericeae were studied as potentially resistant organisms.  Results  In the prospective study, there were 171 nursing home residents. S. pneumoniae was the most frequent causative organsim in both groups. There was no increased frequency of MRSA (0.6% in NHAP vs 0.4% in CAP,p=0.6), P. aeruginosa (0.6% vs 0.5%,p=0.8) or enterobactericeae (2.3% vs 1.2%,p=0.2) in NHAP compared to CAP.  In the systematic review and meta-analysis, 6 studies were identified including 6444 patients. There was no significant increase in the frequency of MRSA (OR 0.28 95% CI 0.03-2.76,p=0.3) or P. aeruginosa (0.63 95% CI 0.31-1.30,p=0.2) but a statistically significant increase in enterobactericeae (1.41 95% CI 1.01-1.97,p=0.04) was identified. Patients with NHAP were more likely to die (3.25 95% CI 2.06-5.15,p  Conclusion  Our findings do not support a change in antibiotic prescribing practices for NHAP patients.
Leucine turnover in patients with nephrotic syndrome
Authors: V S Lim, M Wolfson, K E Yarasheski, M J Flanigan, J D Kopple
Journal: Journal of the American Society of Nephrology (1998)

Whole-body leucine flux was measured in eight patients with nephrotic syndrome and in five healthy subjects by primed-constant infusion of L-[1-13C leucine]. Plasma enrichment of 13C leucine and 13C alpha-keto-isocaproate (13C KIC) was measured by gas chromatography/mass spectrometry, and expired 13CO2 was measured by isotope ration mass spectrometry. Leucine kinetics, calculated from the primary pool enrichment [13C leucine], showed no difference between the nephrotic patients and the control subjects. Kinetics derived from the reciprocal pool [1-13C KIC] enrichment, however, showed that leucine turnover rates were reduced in the nephrotic patients. The values (mumol/kg per h, means +/- SD) comparing the patients and the control subjects are as follows: rate of leucine release from protein degradation, 99 +/- 6 and 117 +/- 12 (P = 0.007); leucine oxidation rate, 15 +/- 7 and 22 +/- 3 (P = 0.04); rate of leucine incorporation into body protein [S], 84 +/- 10 and 95 +/- 6 (P = 0.04); protein turnover rate, 3.99 +/- 0.49 and 4.72 +/- 0.25 g/kg per d (P = 0.007). Nitrogen balance, measured only in the nephrotic patients, showed a mean positive balance of 0.5 g/d. In the nephrotic and control subjects, protein intake levels were 0.84 +/- 0.16 and 1.17 +/- 0.18 g/kg per d (P = 0.002), respectively, and energy intake levels were 33.3 +/- 8.5 and 33.9 +/- 2.4 kcal/kg per d, respectively. Linear correlations between leucine turnover rates and protein intake were highly significant. This study found that nephrotic patients given a modestly protein-restricted diet were able to maintain positive nitrogen balance. Moreover, leucine flux measurements showed downregulation of protein degradation and amino acid oxidation, reflecting appropriate adaptation to a lower protein intake.
Profound effect of normalization on detection of differentially expressed genes in oligonucleotide microarray data analysis
Authors: Reinhard Hoffmann, Thomas Seidl, Martin Dugas
Journal: Genome biology (2002)

Oligonucleotide microarrays measure the relative transcript abundance of thousands of mRNAs in parallel. A large number of procedures for normalization and detection of differentially expressed genes have been proposed. However, the relative impact of these methods on the detection of differentially expressed genes remains to be determined.We have employed four different normalization methods and all possible combinations with three different statistical algorithms for detection of differentially expressed genes on a prototype dataset. The number of genes detected as differentially expressed differs by a factor of about three. Analysis of lists of genes detected as differentially expressed, and rank correlation coefficients for probability of differential expression shows that a high concordance between different methods can only be achieved by using the same normalization procedure.Normalization has a profound influence of detection of differentially expressed genes. This influence is higher than that of three subsequent statistical analysis procedures examined. Algorithms incorporating more array-derived information than gene-expression values alone are urgently needed.
Twelve-month follow-up of psychotherapy for opiate dependence [published erratum appears in Am J Psychiatry 1989 Dec;146(12):1651]
Authors: Woody Ge, McLellan At, Luborsky L, O'Brien Cp
Journal: American Journal of Psychiatry (1987)

To provide information on the long-debated issue of the value of psychotherapy as an addition to paraprofessional counseling services for opiate addicts receiving methadone maintenance, the authors obtained 12-month follow-up data on 93 such patients randomly assigned to a 6-month course of either paraprofessional drug counseling or counseling plus professional psychotherapy. The psychotherapy patients had a significantly better overall status at 7-month follow-up and also at 12-month follow-up, 6 months after the psychotherapy ended. The authors conclude that psychotherapy can be evaluated by using scientific methods and that it can have measurable and sustained benefits in the treatment of opiate addiction.
Low-dose urokinase infusions to treat fibrinous obstruction of venous access devices in cancer patients.
Authors: M K Horne, D J Mayo
Journal: Journal of Clinical Oncology (1997)

PURPOSE This study was undertaken to determine the role of low-dose urokinase infusions in treating fibrinous occlusions of venous access devices (VADs) in cancer patients. PATIENTS AND METHODS Forty-two patients with VAD occlusions refractory to routine urokinase instillations were documented by x-ray (cathetergram) to have fibrin sleeves at the catheter tips. They were randomized to receive infusions of either urokinase (40,000 U/h) or urokinase with heparin (320 U/h) through their catheters. After 1, 3, 6, and 12 hours of treatment, the function of the VADs was reassessed. Whenever the obstruction had been relieved, the infusion was stopped and a repeat cathetergram was performed. The status of the unoccluded catheters was followed to determine the longevity of the restored function. RESULTS Twenty-one catheters were treated with urokinase alone and 21 with the combination of urokinase and heparin. In each group, 16 VADs opened within 12 hours of treatment and five did not. By actuarial analysis, the probability was only 0.28 that a reopened catheter would reocclude within 6 months. CONCLUSION Low-dose urokinase infusions can restore function to the majority of catheters occluded by fibrin sleeves. Adding heparin to the urokinase does not enhance the efficacy of the infusions. The restored function often persists until the VADs are removed.
Prevalence of sleep apnea syndrome in morbidly obese patients
Authors: Elena Ojeda Castillejo, Jorge García Angulo, Jose Miguel Rodriguez Gonzalez-Moro, Soledad Lopez Martin, Gema Sanchez Muñoz, Pilar De Lucas Ramos
Journal: European Respiratory Journal (2013)

Introduction: Obesity is a major risk factor for developing sleep apnea syndrome. CPAP is its treatment. Moreover, the use of CPAP may decrease perioperative complications in patients who have to undergo bariatric surgery.

- Objective: To study the prevalence of OSAS in morbidly obese subjects.

- Methods: We studied all patients who were referred to our unit of sleep disorders with an obesity diagnosis, using the following inclusion criteria: BMI higher than 40, acceptance of polygraphy. All patients answered a clinical questionnaire in order to assess: symptoms of sleep apnea and cardiometabolic comorbidity. Additionally, they all went through a polygraphic or polysomnographic study. The diagnosis of OSA was established with the presence of an AHI higher than 5 and the severity rating was made according to the SEPAR criteria.

- Results: In three years we have studied 292 subjects with the stablished criteria, 115 men, 176 women, average age 47.1 +/-14. Average BMI 46.7. SAHS diagnosis was established in 243 cases (83.5% prevalence) of which 54 (22.2%) had mild OSA, 62 (25.5%) moderate OSA, and 127 (52.2%) severe OSA. In patients with OSA, the Epworth test average result was 7.43 +/-4.5 and in terms of comorbidity, 106 patiens had hipertension, 43.6%, 89 had dyslipidemia (36.6%) and 60 had diabetes (24.6%), 11 had had ischemic events (4.7%) and 5 had cerebrovascular disease (2%).

- Conclusions: Individuals with morbid obesity have a very high prevalence of OSA in the absence of significant hypersomnolence. The need to treat these patients makes us recommend the routinary performance of polygraphic studies, even in paucisymptomatic patients.
Proteogenomic analysis of psoriasis reveals discordant and concordant changes in mRNA and protein abundance
Authors: William R. Swindell, Henriette A. Remmer, Mrinal K. Sarkar, Xianying Xing, Drew H. Barnes, Liza Wolterink, John J. Voorhees, Rajan P. Nair, Andrew Johnston, James T. Elder, Johann E. Gudjonsson
Journal: Genome Medicine (2015)

Background: Psoriasis is a chronic disease characterized by the development of scaly red skin lesions and possible co-morbid conditions.The psoriasis lesional skin transcriptome has been extensively investigated, but mRNA levels do not necessarily reflect protein abundance.The purpose of this study was therefore to compare differential expression patterns of mRNA and protein in psoriasis lesions.Methods: Lesional (PP) and uninvolved (PN) skin samples from 14 patients were analyzed using high-throughput complementary DNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).Results: We identified 4122 differentially expressed genes (DEGs) along with 748 differentially expressed proteins (DEPs).Global shifts in mRNA were modestly correlated with changes in protein abundance (r = 0.40).We identified similar numbers of increased and decreased DEGs, but 4-fold more increased than decreased DEPs.Ribosomal subunit and translation proteins were elevated within lesions, without a corresponding shift in mRNA expression (RPL3, RPS8, RPL11).We identified 209 differentially expressed genes/proteins (DEGPs) with corresponding trends at the transcriptome and proteome levels.Most DEGPs were similarly altered in at least one other skin disease.Psoriasis-specific and non-specific DEGPs had distinct cytokine-response patterns, with only the former showing disproportionate induction by IL-17A in cultured keratinocytes.Conclusions: Our findings reveal global imbalance between the number of increased and decreased proteins in psoriasis lesions, consistent with heightened translation.This effect could not have been discerned from mRNA profiling data alone.High-confidence DEGPs were identified through transcriptome-proteome integration.By distinguishing between psoriasis-specific and non-specific DEGPs, our analysis uncovered new functional insights that would otherwise have been overlooked.
Morphology of a Disease With Features of Malignant Lymphoma in Marmosets and Owl Monkeys Inoculated With <italic>Herpesvirus saimiri</italic>
Authors: Ronald D. Hunt, Luis V. Meléndez, Norval W. King, Charley E. Gilmore, Muthiah D. Daniel, Martha E. Williamson, T. C. Jones
Journal: JNCI Journal of the National Cancer Institute (1970)

Herpesvirus saimiri induced a malignancy resembling malignant lymphoma in cotton-topped marmosets (Saguinus oedipus) and owl monkeys (Aotus trivirgatus). Marked reticulum cell invasion with associated organ replacement occurred in a variety of tissues, but regularly in the liver, kidney, spleen, lymph nodes, and adrenal. Peripheral blood changes developed in some individuals and were characterized by leukocytosis, lymphocytosis, and the presence of immature lymphocytes, lymphoblasts, and reticulum cells. The malignancy developed in every marmoset or owl monkey inoculated with the virus and resulted in death in 13–48 days.