tbuckley/cabot-search huggingface dataset:
Influence of Coagulation Factor X on In Vitro and In Vivo Gene Delivery by Adenovirus (Ad) 5, Ad35, and Chimeric Ad5/Ad35 Vectors
Authors: Jenny A Greig, Suzanne MK Buckley, Simon N Waddington, Alan L Parker, David Bhella, Rebecca Pink, Ahad A Rahim, Takashi Morita, Stuart A Nicklin, John H McVey, Andrew H Baker
Journal: Molecular Therapy (2009)

The binding of coagulation factor X (FX) to the hexon of adenovirus (Ad) 5 is pivotal for hepatocyte transduction. However, vectors based on Ad35, a subspecies B Ad, are in development for cancer gene therapy, as Ad35 utilizes CD46 (which is upregulated in many cancers) for transduction. We investigated whether interaction of Ad35 with FX influenced vector tropism using Ad5, Ad35, and Ad5/Ad35 chimeras: Ad5/fiber(f)35, Ad5/penton(p)35/f35, and Ad35/f5. Surface plasmon resonance (SPR) revealed that Ad35 and Ad35/f5 bound FX with approximately tenfold lower affinities than Ad5 hexon-containing viruses, and electron cryomicroscopy (cryo-EM) demonstrated a direct Ad35 hexon:FX interaction. The presence of physiological levels of FX significantly inhibited transduction of vectors containing Ad35 fibers (Ad5/f35, Ad5/p35/f35, and Ad35) in CD46-positive cells. Vectors were intravenously administered to CD46 transgenic mice in the presence and absence of FX-binding protein (X-bp), resulting in reduced liver accumulation for all vectors. Moreover, Ad5/f35 and Ad5/p35/f35 efficiently accumulated in the lung, whereas Ad5 demonstrated poor lung targeting. Additionally, X-bp significantly reduced lung genome accumulation for Ad5/f35 and Ad5/p35/f35, whereas Ad35 was significantly enhanced. In summary, vectors based on the full Ad35 serotype will be useful vectors for selective gene transfer via CD46 due to a weaker FX interaction compared to Ad5.
Long-Term Follow-Up of Patients With Follicular Lymphoma Receiving Single-Agent Rituximab at Two Different Schedules in Trial SAKK 35/98
Authors: Giovanni Martinelli, Shu-Fang Hsu Schmitz, Urs Utiger, Thomas Cerny, Urs Hess, Simona Bassi, Emmie Okkinga, Roger Stupp, Rolf Stahel, Marc Heizmann, Daniel Vorobiof, Andreas Lohri, Pierre-Yves Dietrich, Emanuele Zucca, Michele Ghielmini
Journal: Journal of Clinical Oncology (2010)

Purpose We report the long-term results of a randomized clinical trial comparing induction therapy with once per week for 4 weeks single-agent rituximab alone versus induction followed by 4 cycles of maintenance therapy every 2 months in patients with follicular lymphoma. Patients and Methods Patients (prior chemotherapy 138; chemotherapy-naive 64) received single-agent rituximab and if nonprogressive, were randomly assigned to no further treatment (observation) or four additional doses of rituximab given at 2-month intervals (prolonged exposure). Results At a median follow-up of 9.5 years and with all living patients having been observed for at least 5 years, the median event-free survival (EFS) was 13 months for the observation and 24 months for the prolonged exposure arm (P &lt; .001). In the observation arm, patients without events at 8 years were 5%, while in the prolonged exposure arm they were 27%. Of previously untreated patients receiving prolonged treatment after responding to rituximab induction, at 8 years 45% were still without event. The only favorable prognostic factor for EFS in a multivariate Cox regression was the prolonged rituximab schedule (hazard ratio, 0.59; 95% CI, 0.39 to 0.88; P = .009), whereas being chemotherapy naive, presenting with stage lower than IV, and showing a VV phenotype at position 158 of the Fc-gamma RIIIA receptor were not of independent prognostic value. No long-term toxicity potentially due to rituximab was observed. Conclusion An important proportion of patients experienced long-term remission after prolonged exposure to rituximab, particularly if they had no prior treatment and responded to rituximab induction.
Safety and efficacy of vaccination against hepatitis B in patients with rheumatoid arthritis
Authors: O Elkayam
Journal: Annals of the Rheumatic Diseases (2002)

<b>Background:</b> Hepatitis B infection and vaccination against it have been implicated in the potential triggering or flare of some autoimmune diseases, including rheumatoid arthritis (RA). However, the safety of hepatitis B vaccination in patients with pre-existing RA is not known. <b>Objectives:</b> To assess the safety and antibody response of immunisation with a recombinant DNA hepatitis B vaccine in patients with RA. <b>Patients and methods:</b> The study comprised 44 patients with RA, of whom 22 received three doses (the second and third dose being given after one and six months) of a recombinant DNA hepatitis B vaccine (study group) and 22 did not receive the vaccine (control group). Both groups had comparable proportions of women and similar mean age (51 years). Clinical assessment before and two and seven months after the first immunisation included evaluation of daytime pain with a 10 cm visual analogue scale, duration of morning stiffness, and number of tender and swollen joints. Erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were measured at each visit. Antibodies to hepatitis B surface antigen (HBsAg) were determined by a commercial enzyme linked immunosorbent assay (ELISA) test kit. <b>Results:</b> Hepatitis B vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease. The measures of disease activity of the patients and controls during the study period did not differ significantly: p=0.76 for daytime pain, p=0.1 for morning stiffness, p=0.24 and p=0.3 for tender and swollen joints respectively, p=0.08 for CRP, and p=0.12 for ESR. Fifteen of the 22 patients responded to vaccination, with an antibody level against HBsAg of 10 IU/l after seven months. Lack of response was associated with older age and higher scores of daytime pain. <b>Conclusions:</b> Hepatitis B vaccination is safe in RA and produces antibodies in 68% of the patients.
INGUINAL ADENITIS IN PRIMARY SYPHILIS IN THE MALE
Authors: W. FOWLER
Journal: British Journal of Dermatology (1948)

Journal Article INGUINAL ADENITIS IN PRIMARY SYPHILIS IN THE MALE Get access W. FOWLER, M.B., Ch.B. W. FOWLER, M.B., Ch.B. Assistant, Department for Venereal Diseases, The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 60, Issue 9, 1 September 1948, Pages 279–282, https://doi.org/10.1111/j.1365-2133.1948.tb11302.x Published: 01 September 1948
Effects of Short-Term Treatment of Hyperlipidemia on Coronary Vasodilator Function and Myocardial Perfusion in Regions Having Substantial Impairment of Baseline Dilator Reverse
Authors: Gordon S. Huggins, Richard C. Pasternak, Nathaniel M. Alpert, Alan J. Fischman, Henry Gewirtz
Journal: Circulation (1998)

We tested the hypothesis that correction of hyperlipidemia improves coronary vasodilator response and maximal perfusion in myocardial regions having substantial impairment of pretreatment vasodilator capacity.Measurements of myocardial blood flow were made with PET [13N]ammonia in 12 patients with ischemic heart disease (11 men; age, 65+/-8 years [mean+/-SD]) at rest and during adenosine at 70 and then 140 microg . kg-1 . min-1 for 5 minutes each before and approximately 4 months after simvastatin treatment (40 mg daily). Simvastatin reduced LDL (171+/-13 before versus 99+/-18 mg/dL after simvastatin, P<0.001) and increased HDL (39+/-8 versus 45+/-9 mg/dL, P<0.05). Myocardial segments were classified on the basis of pretreatment blood flow response to 140 microg . kg-1 . min-1 adenosine as normal (flow >/=2 mL . min-1 . g-1) or abnormal (flow <2 mL . min-1 . g-1). In normal segments, baseline myocardial blood flow (0.95+/-0.32) increased (P<0.001) at both low- (1.62+/-0.81) and high- (2.63+/-0.41) dose adenosine and was unchanged both at rest and with adenosine after simvastatin. In abnormal segments, myocardial blood flow at rest (0. 73+/-0.19) increased at low- (1.06+/-0.59, P<0.02) and high- (1. 29+/-0.33, P<0.01) dose adenosine. After simvastatin, myocardial blood flow increased more compared with pretreatment at both low- (1. 37+/-0.66, P<0.05 versus pretreatment) and high- (1.89+/-0.79, P<0. 01 versus pretreatment) dose adenosine.Short-term lipid-lowering therapy increases stenotic segment maximal myocardial blood flow by approximately 45%. The mechanism involves enhanced, flow-mediated dilation of stenotic epicardial conduit vessels and may account at least in part for the efficacy of lipid lowering in secondary prevention trials and in reducing ischemic episodes in ambulatory patients.
Spanish Diabetes Self-Management With and Without Automated Telephone Reinforcement
Authors: Kate Lorig, Philip L. Ritter, Frank Villa, John D. Piette
Journal: Diabetes Care (2008)

To determine 1) whether participants in the Spanish Diabetes Self-Management Program (SDSMP), when compared at 6 months to randomized control subjects, would demonstrate improvements in health status, health behaviors, and self-efficacy; and 2) whether SDSMP participants receiving monthly automated telephone reinforcement would maintain improvements at 18 months better than those not receiving reinforcement.A total of 567 Spanish-speaking adults with type 2 diabetes were randomized to a usual-care control group or 6-week community-based, peer-led SDSMP. SDSMP participants were re-randomized to receive 15 months of automated telephone messages or no reinforcement. A1C was measured at baseline and 6 and 18 months. All other data were collected by self-administered questionnaires.At 6 months SDSMP participants compared with control subjects demonstrated improvements in A1C (-0.4%), health distress, symptoms of hypo- and hyperglycemia, and self-efficacy (P < 0.05). At 18 months all improvements persisted (P < 0.05). SDSMP participants also demonstrated improvements in self-rated health and communication with physicians, had fewer emergency room visits (-0.18 visits in 6 months, P < 0.05), and trended toward fewer visits to physicians. At 18 months the only difference between reinforced and nonreinforced participants was increased glucose monitoring for the reinforcement group.The SDSMP demonstrated effectiveness in lowering A1C and improving health status. Reinforcement did not add to its effectiveness. Given the high needs of the Spanish-speaking population, the SDSMP deserves consideration for implementation.
Erythropoietin as a Retinal Angiogenic Factor in Proliferative Diabetic Retinopathy
Authors: Daisuke Watanabe, Kiyoshi Suzuma, Shigeyuki Matsui, Masafumi Kurimoto, Junichi Kiryu, Mihori Kita, Izumi Suzuma, Hirokazu Ohashi, Tomonari Ojima, Tomoaki Murakami, Toshihiro Kobayashi, Seiji Masuda, Masaya Nagao, Nagahisa Yoshimura, Hitoshi Takagi
Journal: New England Journal of Medicine (2005)

Although vascular endothelial growth factor (VEGF) is a primary mediator of retinal angiogenesis, VEGF inhibition alone is insufficient to prevent retinal neovascularization. Hence, it is postulated that there are other potent ischemia-induced angiogenic factors. Erythropoietin possesses angiogenic activity, but its potential role in ocular angiogenesis is not established.We measured both erythropoietin and VEGF levels in the vitreous fluid of 144 patients with the use of radioimmunoassay and enzyme-linked immunosorbent assay. Vitreous proliferative potential was measured according to the growth of retinal endothelial cells in vitro and with soluble erythropoietin receptor. In addition, a murine model of ischemia-induced retinal neovascularization was used to evaluate erythropoietin expression and regulation in vivo.The median vitreous erythropoietin level in 73 patients with proliferative diabetic retinopathy was significantly higher than that in 71 patients without diabetes (464.0 vs. 36.5 mIU per milliliter, P<0.001). The median VEGF level in patients with retinopathy was also significantly higher than that in patients without diabetes (345.0 vs. 3.9 pg per milliliter, P<0.001). Multivariate logistic-regression analyses indicated that erythropoietin and VEGF were independently associated with proliferative diabetic retinopathy and that erythropoietin was more strongly associated with the presence of proliferative diabetic retinopathy than was VEGF. Erythropoietin and VEGF gene-expression levels are up-regulated in the murine ischemic retina, and the blockade of erythropoietin inhibits retinal neovascularization in vivo and endothelial-cell proliferation in the vitreous of patients with diabetic retinopathy in vitro.Our data suggest that erythropoietin is a potent ischemia-induced angiogenic factor that acts independently of VEGF during retinal angiogenesis in proliferative diabetic retinopathy.
Comparison of a Real-Time Polymerase Chain Reaction Assay for Lactase Genetic Polymorphism With Standard Indirect Tests for Lactose Maldigestion
Authors: Andrew Szilagyi, Paula Malolepszy, Elise Hamard, Xiaoqing Xue, Nir Hilzenrat, Mary Ponniah, Elizabeth MacNamara, George Chong
Journal: Clinical Gastroenterology and Hepatology (2006)
Caffeine Therapy for Apnea of Prematurity
Authors: Barbara Schmidt, Robin S. Roberts, Peter Davis, Lex W. Doyle, Keith J. Barrington, Arne Ohlsson, Alfonso Solimano, Win Tin
Journal: New England Journal of Medicine (2006)

Methylxanthines reduce the frequency of apnea of prematurity and the need for mechanical ventilation during the first seven days of therapy. It is uncertain whether methylxanthines have other short- and long-term benefits or risks in infants with very low birth weight.We randomly assigned 2006 infants with birth weights of 500 to 1250 g during the first 10 days of life to receive either caffeine or placebo, until drug therapy for apnea of prematurity was no longer needed. We evaluated the short-term outcomes before the first discharge home.Of 963 infants who were assigned to caffeine and who remained alive at a postmenstrual age of 36 weeks, 350 (36 percent) received supplemental oxygen, as did 447 of the 954 infants (47 percent) assigned to placebo (adjusted odds ratio, 0.63; 95 percent confidence interval, 0.52 to 0.76; P<0.001). Positive airway pressure was discontinued one week earlier in the infants assigned to caffeine (median postmenstrual age, 31.0 weeks; interquartile range, 29.4 to 33.0) than in the infants in the placebo group (median postmenstrual age, 32.0 weeks; interquartile range, 30.3 to 34.0; P<0.001). Caffeine reduced weight gain temporarily. The mean difference in weight gain between the group receiving caffeine and the group receiving placebo was greatest after two weeks (mean difference, -23 g; 95 percent confidence interval, -32 to -13; P<0.001). The rates of death, ultrasonographic signs of brain injury, and necrotizing enterocolitis did not differ significantly between the two groups.Caffeine therapy for apnea of prematurity reduces the rate of bronchopulmonary dysplasia in infants with very low birth weight. (ClinicalTrials.gov number, NCT00182312.).
Assessment of the Influence of Asthma Status on Serotype-Specific Antibody Response to Pneumococcal Polysaccharide Antigens
Authors: J.A. Jung, H. Kita, R. Mann, C. Tsigrelis, L.M. Baddour, R.M. Jacobson, T.G. Boyce, Y.J. Juhn
Journal: Journal of Allergy and Clinical Immunology (2009)
Development of Novel ADCs: Conjugation of Tubulysin Analogues to Trastuzumab Monitored by Dual Radiolabeling
Authors: Ruth Cohen, Danielle J. Vugts, Gerard W.M. Visser, Marijke Stigter-van Walsum, Marije Bolijn, Marco Spiga, Paolo Lazzari, Sreejith Shankar, Monica Sani, Matteo Zanda, Guus A.M.S. van Dongen
Journal: Cancer Research (2014)

Tubulysins are highly toxic tubulin-targeting agents with a narrow therapeutic window that are interesting for application in antibody-drug conjugates (ADC). For full control over drug-antibody ratio (DAR) and the effect thereof on pharmacokinetics and tumor targeting, a dual-labeling approach was developed, wherein the drug, tubulysin variants, and the antibody, the anti-HER2 monoclonal antibody (mAb) trastuzumab, are radiolabeled. (131)I-radioiodination of two synthetic tubulysin A analogues, the less potent TUB-OH (IC50 > 100 nmol/L) and the potent TUB-OMOM (IC50, ~1 nmol/L), and their direct covalent conjugation to (89)Zr-trastuzumab were established. Radioiodination of tubulysins was 92% to 98% efficient and conversion to N-hydroxysuccinimide (NHS) esters more than 99%; esters were isolated in an overall yield of 68% ± 5% with radiochemical purity of more than 99.5%. Conjugation of (131)I-tubulysin-NHS esters to (89)Zr-trastuzumab was 45% to 55% efficient, resulting in ADCs with 96% to 98% radiochemical purity after size-exclusion chromatography. ADCs were evaluated for their tumor-targeting potential and antitumor effects in nude mice with tumors that were sensitive or resistant to trastuzumab, using ado-trastuzumab emtansine as a reference. ADCs appeared stable in vivo. An average DAR of 2 and 4 conferred pharmacokinetics and tumor-targeting behavior similar to parental trastuzumab. Efficacy studies using single-dose TUB-OMOM-trastuzumab (DAR 4) showed dose-dependent antitumor effects, including complete tumor eradications in trastuzumab-sensitive tumors in vivo. TUB-OMOM-trastuzumab (60 mg/kg) displayed efficacy similar to ado-trastuzumab emtansine (15 mg/kg) yet more effective than trastuzumab. Our findings illustrate the potential of synthetic tubulysins in ADCs for cancer treatment.
Effect of Imposed Inflation Time on Respiratory Frequency and Hyperinflation in Patients with Chronic Obstructive Pulmonary Disease
Authors: FRANCO LAGHI, JEREMY SEGAL, WILLIAM K. CHOE, MARTIN J. TOBIN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Decreases in ventilator inflation time (Ti,vent) can cause tachypnea, probably as a response to lung inflation. The response may differ in chronic obstructive pulmonary disease (COPD) because time-constant inhomogeneities could foster overdistention of some lung units during early inflation, causing neural inspiratory time to be shorter than in healthy subjects. We tested the hypothesis that a decrease in Ti,vent causes tachypnea, prolongation of exhalation, and a decrease in intrinsic positive end-expiratory pressure (PEEPi). Ten patients with stable COPD received assist-control ventilation through a mouthpiece. Decreases in Ti,vent, achieved through increases in flow from 30 to 90 L/min, increased frequency, from 16.1 ± 1.0 (SE) to 20.8 ± 1.5 breaths/min (p < 0.001), time for exhalation, from 2.1 ± 0.2 to 2.3 ± 0.2 s (p < 0.025), and decreased PEEPi, from 7.0 ± 1.3 to 6.4 ± 1.1 cm H2O (p < 0.01). Decreases in Ti,vent, achieved by decreasing inspiratory pause from 2 to 0 s, increased frequency, from 12.9 ± 0.8 to 18.1 ± 1.6 breaths/min (p < 0.001), time for exhalation, from 2.0 ± 0.2 to 2.6 ± 0.3 s (p < 0.001), and decreased PEEPi, from 6.4 ± 1.1 to 5.5 ± 0.9 cm H2O (p < 0.01). In both experiments, decreases in Ti,vent reduced inspiratory effort (p < 0.01). In conclusion, strategies to reduce Ti,vent in patients with COPD caused tachypnea, yet prolonged the time for exhalation with consequent decrease in PEEPi.
On-Chip Biomedical Imaging
Authors: Z. Gorocs, A. Ozcan
Journal: IEEE Reviews in Biomedical Engineering (2012)

Lab-on-a-chip systems have been rapidly emerging to pave the way toward ultra-compact, efficient, mass producible and cost-effective biomedical research and diagnostic tools. Although such microfluidic and microelectromechanical systems have achieved high levels of integration, and are capable of performing various important tasks on the same chip, such as cell culturing, sorting and staining, they still rely on conventional microscopes for their imaging needs. Recently, several alternative on-chip optical imaging techniques have been introduced, which have the potential to substitute conventional microscopes for various lab-on-a-chip applications. Here we present a critical review of these recently emerging on-chip biomedical imaging modalities, including contact shadow imaging, lens-free holographic microscopy, fluorescent on-chip microscopy and lens-free optical tomography.
Cell or Cell Membrane-Based Drug Delivery Systems
Authors: Songwei Tan, Tingting Wu, Dan Zhang, Zhiping Zhang
Journal: Theranostics (2015)

Natural cells have been explored as drug carriers for a long period.They have received growing interest as a promising drug delivery system (DDS) until recently along with the development of biology and medical science.The synthetic materials, either organic or inorganic, are found to be with more or less immunogenicity and/or toxicity.The cells and extracellular vesicles (EVs), are endogenous and thought to be much safer and friendlier.Furthermore, in view of their host attributes, they may achieve different biological effects and/or targeting specificity, which can meet the needs of personalized medicine as the next generation of DDS.In this review, we summarized the recent progress in cell or cell membrane-based DDS and their fabrication processes, unique properties and applications, including the whole cells, EVs and cell membrane coated nanoparticles.We expect the continuing development of this cell or cell membrane-based DDS will promote their clinic applications.
Sclerosing lipogranuloma of the male genitalia: ultrastructural study
Authors: A. CLAUDY, F. GARCIER, D. SCHMITT
Journal: British Journal of Dermatology (1981)

SUMMARY Ultrastructural study of a case of sclerosing lipogranuloma showed a predominantly histiocytic-like cell infiltrate with numerous intracytoplasmic vacuoles of varied sizes without any limiting membrane and located in the deep dermis and subcutaneous fat. Fibroblasts appeared normal. Polymorphonuclear cells and macrophages were absent. This appearance was different from that described in ‘classical’ phagocytosis, mucopolysaccharidoses or polyvinylpyrrolidone storage syndrome.
PCTAIRE1 Phosphorylates p27 and Regulates Mitosis in Cancer Cells
Authors: Teruki Yanagi, Maryla Krajewska, Shu-ichi Matsuzawa, John C. Reed
Journal: Cancer Research (2014)

Abstract PCTAIRE1 is distant relative of the cyclin-dependent kinase family that has been implicated in spermatogenesis and neuronal development, but it has not been studied in cancer. Here, we report that PCTAIRE1 is expressed in prostate, breast, and cervical cancer cells, where its RNAi-mediated silencing causes growth inhibition with aberrant mitosis due to defects in centrosome dynamics. PCTAIRE1 was not similarly involved in proliferation of nontransformed cells, including diploid human IMR-90 fibroblasts. Through yeast two-hybrid screening, we identified tumor suppressor p27 as a PCTAIRE1 interactor. In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PCTAIRE1 silencing modulated Ser10 phosphorylation on p27 and led to its accumulation in cancer cells but not in nontransformed cells. In a mouse xenograft model of PPC1 prostate cancer, conditional silencing of PCTAIRE1 restored p27 protein expression and suppressed tumor growth. Mechanistic studies in HeLa cells showed that PCTAIRE1 phosphorylates p27 during the S and M phases of the cell cycle. Notably, p27 silencing was sufficient to rescue cells from mitotic arrest caused by PCTAIRE1 silencing. Clinically, PCTAIRE1 was highly expressed in primary breast and prostate tumors compared with adjacent normal epithelial tissues. Together our findings reveal an unexpected role for PCTAIRE1 in regulating p27 stability, mitosis, and tumor growth, suggesting PCTAIRE1 as a candidate cancer therapeutic target. Cancer Res; 74(20); 5795–807. ©2014 AACR.