tbuckley/cabot-search huggingface dataset:
Immune modulation effects of concomitant temozolomide and radiation therapy on peripheral blood mononuclear cells in patients with glioblastoma multiforme
Authors: C. E. Fadul, J. L. Fisher, J. Gui, T. H. Hampton, A. L. Cote, M. S. Ernstoff
Journal: Neuro-Oncology (2011)

Concomitant radiation therapy (RT) and temozolomide (TMZ) therapy after surgery is the standard treatment for glioblastoma multiforme (GBM). Radiation and chemotherapy can affect the immune system with implications on subsequent immune therapy. Therefore, we examined the phenotype and function of peripheral blood mononuclear cells in 25 patients with GBM prior to and 4 weeks after treatment with RT-TMZ using multicolor flow cytometry, as well as in vitro CD4+ regulatory T cell (Treg) suppressor and dendritic cell maturation assays. RT-TMZ induced significant lymphopenia, with a decrease in total CD4+ T cells, but did not significantly change monocyte counts. The proportion of functional Treg cells increased after treatment, whereas their absolute numbers remained stable. There was also a measurable decrease in the proportion of CD8+CD56+ and absolute number of CD3−CD56+ effector cells. Posttherapy monocytes retained the ability to mature into dendritic cells. Treatment with RT-TMZ is associated with changes in regulatory and effector peripheral blood mononuclear cells that tilt the balance towards an immune suppressive state. This shift can affect the outcome of immune therapy following RT-TMZ treatment and should be considered in the design of future combination therapy regimens.
Stem Cells: Controlling Major Cellular Processes of Human Mesenchymal Stem Cells using Microwell Structures (Adv. Healthcare Mater. 12/2014)
Authors: Xun Xu, Weiwei Wang, Karl Kratz, Liang Fang, Zhengdong Li, Andreas Kurtz, Nan Ma, Andreas Lendlein
Journal: Advanced Healthcare Materials (2014)

The geometry of polymeric matrices is a powerful tool to control cell behavior. On page 1991 N. Ma, A. Lendlein, and co-workers demonstrate human adipose-derived stem cells that show ROCK pathway-mediated differences in their response to square- and round-shaped microwells with respect to their morphology, proliferation, migration, and differentiation. Phagocytes react differently to spherical and ellipsoid microparticles, which now can shift their shape upon stimulation due to an internal polymer micronetwork structure.
Mitochondrial DNA Quantity Increases with Histopathologic Grade in Premalignant and Malignant Head and Neck Lesions
Authors: Michael M. Kim, John D. Clinger, Brett G. Masayesva, Patrick K. Ha, Marianna L. Zahurak, William H. Westra, Joseph A. Califano
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Mitochondria are highly susceptible to oxidative damage. Although mitochondrial function decreases with oxidative damage, overall mitochondrial DNA (mtDNA) content increases to compensate for general mitochondrial dysfunction. We performed quantitative polymerase chain reaction for genes specific to mitochondrial and nuclear genomes to investigate relative mitochondrial abundance in a spectrum of dysplastic head and neck lesions. Experimental Design: DNA from mild, moderate, and severe dysplasias, as well as invasive tumors and normal mucosal cells, was extracted. Using quantitative polymerase chain reaction, mitochondrial to nuclear DNA ratios were determined by quantification of cytochrome c oxidase subunit 1 (CoxI) and β-actin genes. Results: Mean CoxI/β-actin DNA ratios for mild, moderate, and severe premalignant lesions were 0.0529, 0.0607, and 0.1021, respectively. The mean ratio for the normal mucosal cells contained in saliva was 0.0537, whereas the mean ratio for tumors was 0.1667. As a whole, our experimental model demonstrated significance (P = 0.0358). Comparisons between individual categories showed borderline significance when compared with the normal group, with P values of 0.0673, 0.0747, and 0.0824 for moderate and severe dysplasia and invasive tumor, respectively. Conclusions: Head and neck squamous cell carcinomas arise through premalignant intermediates and may be merely morphologic manifestations of accumulated genetic alterations. In keeping with this molecular tumor progression model, our study shows that mtDNA increases according to histopathologic grade, a phenomenon that may be a feedback mechanism that compensates for a generalized decline in respiratory chain function. Therefore, high mtDNA content may be another marker of genetic alteration, a measure of relative DNA injury, and a surrogate measure of histopathologic grade.
Differential cytokine induction by the human skin–associated autoallergen thioredoxin in sensitized patients with atopic dermatitis and healthy control subjects
Authors: Susanne Hradetzky, Lennart Matthias Roesner, Annice Heratizadeh, Reto Crameri, Mattia Garbani, Annika Scheynius, Thomas Werfel
Journal: Journal of Allergy and Clinical Immunology (2014)
Discovery of Cyanophage Genomes Which Contain Mitochondrial DNA Polymerase
Authors: Yi-Wah Chan, Remus Mohr, Andrew D. Millard, Antony B. Holmes, Anthony W. Larkum, Anna L. Whitworth, Nicholas H. Mann, David J. Scanlan, Wolfgang R. Hess, Martha R. J. Clokie
Journal: Molecular Biology and Evolution (2011)

DNA polymerase γ is a family A DNA polymerase responsible for the replication of mitochondrial DNA in eukaryotes. The origins of DNA polymerase γ have remained elusive because it is not present in any known bacterium, though it has been hypothesized that mitochondria may have inherited the enzyme by phage-mediated nonorthologous displacement. Here, we present an analysis of two full-length homologues of this gene, which were found in the genomes of two bacteriophages, which infect the chlorophyll-d containing cyanobacterium Acaryochloris marina. Phylogenetic analyses of these phage DNA polymerase γ proteins show that they branch deeply within the DNA polymerase γ clade and therefore share a common origin with their eukaryotic homologues. We also found homologues of these phage polymerases in the environmental Community Cyberinfrastructure for Advanced Microbial Ecology Research and Analysis (CAMERA) database, which fell in the same clade. An analysis of the CAMERA assemblies containing the environmental homologues together with the filter fraction metadata indicated some of these assemblies may be of bacterial origin. We also show that the phage-encoded DNA polymerase γ is highly transcribed as the phage genomes are replicated. These findings provide data that may assist in reconstructing the evolution of mitochondria.
Feasibility of Preoperative Chemotherapy With or Without Radiation Therapy in Localized Soft Tissue Sarcomas of Limbs and Superficial Trunk in the Italian Sarcoma Group/Grupo Español de Investigación en Sarcomas Randomized Clinical Trial: Three Versus Five Cycles of Full-Dose Epirubicin Plus Ifosfamide
Authors: Elena Palassini, Stefano Ferrari, Paolo Verderio, Antonino De Paoli, Javier Martin Broto, Vittorio Quagliuolo, Alessandro Comandone, Claudia Sangalli, Emanuela Palmerini, Antonio Lopez-Pousa, Rita De Sanctis, Stefano Bottelli, Michela Libertini, Piero Picci, Paolo G. Casali, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2015)

We report on feasibility of preoperative chemotherapy with or without radiation therapy (RT) in the context of a phase III randomized clinical trial involving localized, high-risk, soft tissue sarcomas.Of 321 eligible patients, 161 were randomly assigned to three preoperative cycles of epirubicin 120 mg/m(2) plus ifosfamide 9 g/m(2), and 160 were randomly assigned to three preoperative plus two postoperative cycles. Among them, 303 patients were included in this analysis; 169 were male and 134 were female, with a median age of 48 years (range, 15 to 79 years). One hundred fifty-two patients received concurrent RT preoperatively at a total dose of 44 to 50 Gy. Preoperative chemotherapy-related hematologic toxicity and early postoperative complications were reported. The influence of RT, age, and sex on hematologic grade 3 or 4 toxicities and wound complications was analyzed. Chemotherapeutic dose intensity (DI) was analyzed.Among the patients, 61.4%, 22.4%, and 23.8% experienced, grade 4 leucopenia, grade 3 or 4 anemia, and grade 3 or 4 thrombocytopenia, respectively. Respective rates were 66.4%, 24.3%, and 31.6% when RT was added preoperatively, and 56.3%, 20.5%, and 15.9% when preoperative chemotherapy was administered alone. Patient age affected grade 3 or 4 thrombocytopenia. Grade 4 leucopenia and grade 3 or 4 anemia presented 2.5 times more frequently in female patients than in male patients. Wound complications were observed in 13.5% of patients: 17% with preoperative RT and 10% without. Chemotherapeutic DI was greater than 90%, even in patients receiving preoperative RT and in patients age 65 years or older.This preoperative chemotherapy is feasible and can also be proposed for selected elderly patients. Grade 3 or 4 hematologic toxicity was common, but DI was excellent. Concurrent preoperative RT is safe, although an increased rate of grade 4 thrombocytopenia and limited increase in wound complications may be observed.
Borderline Personality Disorder: Ontogeny of a Diagnosis
Authors: John G. Gunderson
Journal: American Journal of Psychiatry (2009)

Objective: The purpose of this article is to describe the development of the borderline personality disorder diagnosis, highlighting both the obstacles encountered and the associated achievements. Method: On the basis of a review of the literature, the author provides a chronological account of the borderline construct in psychiatry, summarizing progress in decade-long intervals. Results: Borderline personality disorder has moved from being a psychoanalytic colloquialism for untreatable neurotics to becoming a valid diagnosis with significant heritability and with specific and effective psychotherapeutic treatments. Nonetheless, patients with this disorder pose a major public health problem while they themselves remain highly stigmatized and largely neglected. Conclusions: Despite remarkable changes in our knowledge about borderline personality disorder, increased awareness involving much more education and research is still needed. Psychiatric institutions, professional organizations, public policies, and reimbursement agencies need to prioritize this need.
Techniques for assessing teratogenic effects: epidemiology.
Authors: J W Flynt
Journal: Environmental Health Perspectives (1976)

Epidemiologic studies of malformations can aid in the understanding of human teratogenesis. Employing a variety of approaches epidemiology can develop or test hypotheses concerning possible causes or through surveillance provide data useful for a variety of purposes. Drawing heavily upon our experiences at the Center for Disease Control, this paper reviews some concepts and uses of epidemiology in studies of human teratogenesis.
Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations
Authors: L. Decoster, K. Van Puyvelde, S. Mohile, U. Wedding, U. Basso, G. Colloca, S. Rostoft, J. Overcash, H. Wildiers, C. Steer, G. Kimmick, R. Kanesvaran, A. Luciani, C. Terret, A. Hurria, C. Kenis, R. Audisio, M. Extermann
Journal: Annals of Oncology (2014)
Operation for Severe Hypospadias
Authors: R. H. Russell
Journal: BMJ (1900)

dix invaginated into the cmacum in such a way that only a very siall portion of its distal extremity was visible.Its wall and the wall of the cacum over a circular area arouad it were hard and indurated.The appendix except for this was apparently healthy and contained no con- cretion; it was removed and the abdomen closed.After-History.-The wound was dressed and the stitches removed on September 7th, and the boy was discharged on the 21st, having had no pain since the operation.
Results of Therapy for Acute Lymphoblastic Leukemia in Black and White Children
Authors: Ching Hon Pui, John T. Sandlund, Deqing Pei, Gaston K. Rivera, Scott C. Howard, Raul C. Ribeiro, Jeffrey E. Rubnitz, Bassem I. Razzouk, Melissa M. Hudson, Cheng Cheng, Susana C. Raimondi, Frederick G. Behm, James R. Downing, Mary V. Relling, William E. Evans
Journal: JAMA (2003)

ContextTreatment results for acute lymphoblastic leukemia (ALL) clearly have improved over the past decade, but black children have not fared as well as white children in large national trials.ObjectiveTo compare the clinical outcomes of therapy for black and white children with ALL treated at a single institution.Design, Setting, and PatientsA retrospective analysis of 412 children and adolescents (68 black, 338 white, and 6 other race) with newly diagnosed ALL who were treated consecutively at a pediatric cancer center in Memphis, Tenn. Patients were enrolled from December 1991 to July 1998 in successive Total Therapy studies regardless of race, ethnicity, or ability to pay and received risk-directed therapy according to stringent criteria.InterventionsAll patients received the same intensive, remission-induction therapy followed by 120 weeks of risk-assigned postremission therapy that included reinduction treatment, pulses of high-dose methotrexate, and early intensification of intrathecal chemotherapy.Main Outcome MeasuresEvent-free and overall survival rates for black and white children were estimated by the method of Kaplan and Meier and compared with the Mantel-Haenszel test and by Cox proportional hazards regression analysis, adjusting for known prognostic factors.ResultsThe 68 black children were significantly more likely than the 338 white children to have higher-risk prognostic features, including an initial leukocyte count greater than 100 × 103/µL, a T-cell immunophenotype, and the t(1;19) chromosomal translocation with E2A-PBX1 fusion, and were less likely to have hyperdiploid blast cells, a favorable prognostic factor in childhood ALL. However, the clinical outcomes for these 2 cohorts were not significantly different: 5-year event-free and overall survival rates were 80.7% (95% confidence interval [CI], 70.3%-91.1%) and 86.2% (95% CI, 77.2%-95.2%) for black children vs 79.4% (95% CI, 74.7%-84.1%) and 85.0% (95% CI, 80.9%-89.1%) for white children. Ten-year results also were comparable, but the CIs were wide because of the small numbers of patients who had been followed up for 10 years or more. The lack of a racial effect on the long-term outcome of therapy was still apparent in a multivariate Cox regression analysis, adjusting for sex, age, presenting leukocyte count, leukemic cell DNA index, immunophenotype, and central nervous system status.ConclusionWith equal access to effective antileukemic therapy, black and white children with ALL can expect the same high rate of cure.
Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury
Authors: Ji Hae Seo, Nobukazu Miyamoto, Kazuhide Hayakawa, Loc-Duyen D. Pham, Takakuni Maki, Cenk Ayata, Kyu-Won Kim, Eng H. Lo, Ken Arai
Journal: Journal of Clinical Investigation (2013)

Oligodendrocyte precursor cells (OPCs) are thought to maintain homeostasis and contribute to long-term repair in adult white matter; however, their roles in the acute phase after brain injury remain unclear. Mice that were subjected to prolonged cerebral hypoperfusion stress developed white matter demyelination over time. Prior to demyelination, we detected increased MMP9 expression, blood-brain barrier (BBB) leakage, and neutrophil infiltration in damaged white matter. Notably, at this early stage, OPCs made up the majority of MMP9-expressing cells. The standard MMP inhibitor GM6001 reduced the early BBB leakage and neutrophil infiltration, indicating that OPC-derived MMP9 induced early BBB disruption after white matter injury. Cell-culture experiments confirmed that OPCs secreted MMP9 under pathological conditions, and conditioned medium prepared from the stressed OPCs weakened endothelial barrier tightness in vitro. Our study reveals that OPCs can rapidly respond to white matter injury and produce MMP9 that disrupts the BBB, indicating that OPCs may mediate injury in white matter under disease conditions.
Hrd1 and ER-Associated Protein Degradation, ERAD, Are Critical Elements of the Adaptive ER Stress Response in Cardiac Myocytes
Authors: Shirin Doroudgar, Mirko Völkers, Donna J. Thuerauf, Mohsin Khan, Sadia Mohsin, Jonathan L. Respress, Wei Wang, Natalie Gude, Oliver J. Müller, Xander H.T. Wehrens, Mark A. Sussman, Christopher C. Glembotski
Journal: Circulation Research (2015)

Hydroxymethyl glutaryl-coenzyme A reductase degradation protein 1 (Hrd1) is an endoplasmic reticulum (ER)-transmembrane E3 ubiquitin ligase that has been studied in yeast, where it contributes to ER protein quality control by ER-associated degradation (ERAD) of misfolded proteins that accumulate during ER stress. Neither Hrd1 nor ERAD has been studied in the heart, or in cardiac myocytes, where protein quality control is critical for proper heart function.The objective of this study were to elucidate roles for Hrd1 in ER stress, ERAD, and viability in cultured cardiac myocytes and in the mouse heart, in vivo.The effects of small interfering RNA-mediated Hrd1 knockdown were examined in cultured neonatal rat ventricular myocytes. The effects of adeno-associated virus-mediated Hrd1 knockdown and overexpression were examined in the hearts of mice subjected to pressure overload-induced pathological cardiac hypertrophy, which challenges protein-folding capacity. In cardiac myocytes, the ER stressors, thapsigargin and tunicamycin increased ERAD, as well as adaptive ER stress proteins, and minimally affected cell death. However, when Hrd1 was knocked down, thapsigargin and tunicamycin dramatically decreased ERAD, while increasing maladaptive ER stress proteins and cell death. In vivo, Hrd1 knockdown exacerbated cardiac dysfunction and increased apoptosis and cardiac hypertrophy, whereas Hrd1 overexpression preserved cardiac function and decreased apoptosis and attenuated cardiac hypertrophy in the hearts of mice subjected to pressure overload.Hrd1 and ERAD are essential components of the adaptive ER stress response in cardiac myocytes. Hrd1 contributes to preserving heart structure and function in a mouse model of pathological cardiac hypertrophy.
Treatment Failures With Whole-Body Extract Therapy of Insect Sting Allergy
Authors: David B. K. Golden, John Langlois, Martin D. Valentine, Anne Kagey-Sobotka, Lawrence M. Lichtenstein
Journal: JAMA (1981)

Whole-body extracts (WBEs) remain in widespread use for therapy of insect sting anaphylaxis two years after the approval of Hymenoptera venoms. We have reviewed our experience with WBEs in our patient population. Of 250 patients who received WBE, 115 had subsequent stings. Systemic allergic reactions occurred in 65% large local reactions in 23%, and no reaction in 12%. There was no consistent change in the severity of systemic reactions during WBE treatment. Systemic reaction occurred less commonly in younger persons or after at least two years of WBE treatment. We conclude that WBE is not effective for the prevention of allergic insect sting reactions. The natural history of the disease may account for its apparent efficacy in young people or those having prolonged WBE therapy. Venom immunotherapy is safe and rapidly effective and is the only protective treatment recommended.
Estrogen-regulated miRNA-19b modulates the expression of secretory leukoprotease inhibitor in monocytes
Authors: Paul McKiernan, Sanjay Chotirmall, Sally-Ann Cryan, Noel G. McElvaney, Catherine Greene
Journal: European Respiratory Journal (2013)

Estrogen (17β-estradiol, E2) influences the progression of many lung diseases including the gender dichotomy that exists in cystic fibrosis (CF). We hypothesize that E2 modulates the inflammatory response of circulating innate immune cells through microRNA (miR) based modulation of secretory leucoprotease inhibitor (SLPI), a multifunctional antiprotease. Monocytic cells (THP-1, U937) were treated with 10 nM E2 or ethanol vehicle control and miRs that were differentially expressed were identified using Taqman Low Density Array. Cells were transfected with premiRs (miR mimics) or antimiRs for 48 hours. SLPI mRNA levels were quantified by qRT-PCR. Luciferase activity was measured in cells co-transfected with premiRs and wild type or ΔmiR-19 binding site SLPI 3’UTR reporter constructs. PremiRs were encapsulated in poly(lactic-co-glycolic acid) based microparticles for delivery to monocyte/macrophage lineage. SLPI expression is downregulated in response to E2 in monocytic cells. miR profiling indicates that miR-19a/b, predicted in silico to directly target SLPI mRNA are upregulated by E2. Transfection of U937s with premiR-19b reduced SLPI expression levels; miR-19b antimiRs had a reciprocal effect. Luciferase assay confirmed that miR-19b directly targets SLPI mRNA by binding to its 3’UTR. Encapsulation of fluorescent or miR-19b miR mimics produced microparticles with an aerodynamic diameter of 2-3 µm suitable for delivery to monocytic cells. E2 decreases expression of SLPI in monocytic cells via changes in miRNA expression, in particular miR-19. Microparticles have the potential to be used to deliver miR modulators of SLPI into monocytic cells.  Supported by HRB PhD/2007/11.
Can the Parieto-Frontal Integration Theory be extended to account for individual differences in skilled and expert performance in everyday life?
Authors: Roy W. Roring, Kiruthiga Nandagopal, K. Anders Ericsson
Journal: Behavioral and Brain Sciences (2007)

Abstract Performance on abstract unfamiliar tasks used to measure intelligence has not been found to correlate with individual differences in highly skilled and expert performance. Given that cognitive and neural structures and regions mediating performance change as skill increases, the structures highlighted by parieto-frontal integration theory are unlikely to account for individual differences in skilled cognitive achievement in everyday life.
Facial thermography during nasal provocation tests with histamine and allergen
Authors: M. Seppey, C. Hessler, M. Bruchez, M. Savary, A. Pécoud
Journal: Allergy (1993)

Changes of skin temperature (T degree) of the nose area during nasal provocation tests with histamine and allergen were followed by means of an infrared thermography camera. By a colimator system in which temperatures measured on a given surface can be integrated and averaged, thermography allows the continuous and quantitative recording of the temperature during the whole procedure in a completely noninvasive way. In 10 normal subjects, increasing doses of histamine induced a dose-dependent rise of the nose external temperature. No significant change was observed with the vehicle solution. In six subjects allergic to grass pollen, the nebulization of increasing concentrations of a pollen extract induced a dose-dependent rise in T degree. The T degree rise observed after histamine or allergen corresponded to a marked nasal obstruction. The nebulization of the highest dose of the pollen extract did not induce any T degree rise in six nonallergic subjects. The continuous recording of the skin temperature by a noninvasive method might yield additional information on the vascular changes rapidly occurring during nasal challenges.