tbuckley/cabot-search huggingface dataset:
Systemic Delivery of<i>Salmonella typhimurium</i>Transformed with IDO shRNA Enhances Intratumoral Vector Colonization and Suppresses Tumor Growth
Authors: Céline A. Blache, Edwin R. Manuel, Teodora I. Kaltcheva, Andrea N. Wong, Joshua D.I. Ellenhorn, Bruce R. Blazar, Don J. Diamond
Journal: Cancer Research (2012)

Abstract Generating antitumor responses through the inhibition of tumor-derived immune suppression represents a promising strategy in the development of cancer immunotherapeutics. Here, we present a strategy incorporating delivery of the bacterium Salmonella typhimurium (ST), naturally tropic for the hypoxic tumor environment, transformed with a small hairpin RNA (shRNA) plasmid against the immunosuppressive molecule indoleamine 2,3-dioxygenase 1 (shIDO). When systemically delivered into mice, shIDO silences host IDO expression and leads to massive intratumoral cell death that is associated with significant tumor infiltration by polymorphonuclear neutrophils (PMN). shIDO-ST treatment causes tumor cell death independently of host IDO and adaptive immunity, which may have important implications for use in immunosuppressed patients with cancer. Furthermore, shIDO-ST treatment increases reactive oxygen species (ROS) produced by infiltrating PMNs and, conversely, PMN immunodepletion abrogates tumor control. Silencing of host IDO significantly enhances S. typhimurium colonization, suggesting that IDO expression within the tumor controls the immune response to S. typhimurium. In summary, we present a novel approach to cancer treatment that involves the specific silencing of tumor-derived IDO that allows for the recruitment of ROS-producing PMNs, which may act primarily to clear S. typhimurium infection, but in the process also induces apoptosis of surrounding tumor tissue resulting in a vigorous antitumor effect. Cancer Res; 72(24); 6447–56. ©2012 AACR.
Infratentorial craniospinal irradiation for von Hippel-Lindau: a retrospective study supporting a new treatment for patients with CNS hemangioblastomas
Authors: C. B. Simone, R. R. Lonser, J. Ondos, E. H. Oldfield, K. Camphausen, N. L. Simone
Journal: Neuro-Oncology (2011)

Patients with von Hippel–Lindau (VHL) syndrome with diffuse CNS hemangioblastomas have morbidity related to their disease and require a lifetime of surgical resections. Ninety-seven percent of tumors progress, and 5-year surgery rates are 20%–60%. Stereotactic radiosurgery and fractionated radiotherapy have had limited success. For the first time, we have used infratentorial craniospinal radiation therapy (ICSRT) for VHL patients with CNS hemangioblastomas. Consecutive VHL patients treated at the National Institutes of Health with radiographic evidence of hemangioblastomas were included if they received ICSRT. Patients underwent neurologic examinations and imaging at 3- to 12-month intervals. Seven patients with 84 hemangioblastomas met eligibility criteria. ICSRT was commonly administered to 43.2 Gy in 24 fractions. Mean pre-ICSRT tumor volume was 5.48 cm3. At a mean follow-up of 73.8 months, mean post-ICSRT tumor volume was 6.87 cm3, and 91 tumors were identified. Complete radiographic resolution was achieved in 17.9% of lesions. Although many patients were no longer optimal surgical candidates, only 4 surgeries were needed for symptomatic lesions after ICSRT, compared with 33 prior. Acute toxicity was mild and no patient developed grade ≥1 late spinal cord toxicity according to the criteria of the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer, despite the high dose that the entire spinal cord received. Clinical and radiographic stability or resolution was demonstrated in the majority of tumors. Tumor growth rate in this study was less than reported in natural history studies, and the rate of surgical intervention was reduced. ICSRT was well tolerated, can decrease hemangioblastoma growth rate, and is a potential therapeutic option for VHL patients that warrants further investigation.
Glucose Production in Pregnant Women at Term Gestation
Authors: Satish C. Kalhan, Larry J. D'Angelo, Samuel M. Savin, Peter A. J. Adam
Journal: Journal of Clinical Investigation (1979)

The effects of pregnancy and diabetes on systemic glucose production rates and the sources of glucose for the human fetus in utero were evaluated in five normal, four gestationally diabetic, and one insulin-dependent diabetic subject undergoing elective caesarean section at term gestation. Five normal nonpregnant women were studied for comparison. Systemic glucose production rates were measured with stable tracer [1-13C]glucose according to the prime-constant rate infusion technique. Even though the plasma glucose concentration during normal pregnancy had declined as compared with the nonpregnant subjects (P < 0.0005), the systemic glucose production rate was 16% greater, a rate sufficient to provide the glucose requirement of the fetus at term gestation. The decline in glucose concentration could be the result of an increase in apparent volume of distribution of glucose. Systemic glucose production rates in well-controlled, gestationally diabetic subjects were similar to those in normal pregnant subjects (2.07±0.53 vs. 2.42±0.51 mg/kg·min). The sources of glucose for the human fetus at term gestation were evaluated by comparing (a) natural variation in 13C:12C ratio of plasma glucose and (b) enriched 13C:12C ratio of plasma glucose during [1-13C]glucose infusion in maternal and fetal blood at delivery in both normal and diabetic subjects. These data showed that the fetal glucose pool was in equilibrium with the maternal glucose pool in both normal and diabetic subjects, indicating that a brief maternal fast did not initiate systemic glucose production in human fetus. A materno-fetal gradient was observed for betahydroxybutyrate.
In vitro and in vivo responses of different treating agents against wilt disease of safflower
Authors: M. Govindappa, V. Ravishankar Rai, S. Lokesh
Journal: Journal of Clinical Oncology (2011)

In safflower Anucop, captan and Mancozeb M-45 were found extremely effective in reducingFusarium oxysporum f.sp. carthami wilt. The seed treatments improved seed germination, seedling vigour and plant stand. Due to these treatments many of the seed-borne fungi failed to express in the normal way. Bioagents formulations viz., Trichoderma harzianum, Bacillus subtilis and Pseudomonas fluorescens reduced the wilt incidence both under greenhouse and field conditions, thereby enhancing the growth of the seedlings. These antagonists significantly reduced the population of Fusarium oxysporum f.sp. carthami, increased the seed germination and seedling vigour. Leaf extracts of Becopa monniera andAdathoda vasica were found effective in the control of safflower wilt. Comparatively B. monniera enhanced the seed germination and quality parameters of plants both under greenhouse and field conditions and also effectively suppressed the wilt up to flowering.

	 

	Key words: Fungicides, bioagents, plant extracts, Fusarium oxysporum f.sp. carthami, disease management.
Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B
Authors: Ching-Lung Lai, Sang Hoon Ahn, Kwan Sik Lee, Soon Ho Um, Mong Cho, Seung Kew Yoon, Jin-Woo Lee, Neung Hwa Park, Young-Oh Kweon, Joo Hyun Sohn, Jiyoon Lee, Jeong-Ae Kim, Kwang-Hyub Han, Man-Fung Yuen
Journal: Gut (2013)

<h3>Background</h3> Besifovir (LB80380) is an acyclic nucleotide phosphonate effective in hepatitis B virus (HBV) DNA suppression for both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients in preliminary studies. <h3>Design</h3> We aimed to compare the safety and antiviral activity of two doses of besifovir (90 mg and 150 mg daily) with entecavir 0.5 mg daily in CHB patients. 114 patients were randomised to receive besifovir 90 mg daily (n=36), besifovir 150 mg daily (n=39) or entecavir 0.5 mg daily (n=39). HBV DNA and liver biochemistry, including serum L-carnitine levels, were monitored. <h3>Results</h3> At week 48, in the intention-to-treat population, the proportion of patients achieving undetectable HBV DNA (&lt;20 IU/mL) were 63.6%, 62.9% and 58.3%, respectively (p&gt;0.05). The serum mean log<sub>10</sub> HBV DNA changes from baseline for the HBeAg-positive patients were −5.84, −5.91 and −6.18, respectively; and for the HBeAg-negative patients were −4.65, −4.55 and −4.67, respectively (p&gt;0.05). There were no differences in the proportions of patients achieving normalisation of alanine aminotransferase (91.7%, 76.9%, 89.7%, respectively) and HBeAg seroconversion (11.11%, 15%, 9.52%, respectively) among all three groups. None of the patients had resistant mutations or increase in serum creatinine of &gt;0.5 mg/dL from baseline. 64 (94.1%) patients on besifovir had lowering of serum L-carnitine (not tested in entecavir patients). L-carnitine levels returned to normal with carnitine supplement. <h3>Conclusions</h3> At 48 weeks, 90 mg and 150 mg daily of besifovir were non-inferior to entecavir 0.5 mg daily in treatment-naive CHB patients. The only significant side effect of besifovir was L-carnitine depletion, requiring carnitine supplementation.
Estrogen Receptor/Progesterone Receptor-Negative Breast Cancers of Young African-American Women Have a Higher Frequency of Methylation of Multiple Genes than Those of Caucasian Women1
Authors: Jyoti Mehrotra, M. Michelle Ganpat, Yasmine Kanaan, Mary Jo Fackler, Megan McVeigh, Jaana Lahti-Domenici, Kornelia Polyak, Pedram Argani, Tammy Naab, Elizabeth Garrett, Giovanni Parmigiani, Carolyn Broome, Saraswati Sukumar
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To provide a molecular rationale for negative prognostic factors more prevalent in African-American (AA) than Caucasian (Cau) women, we investigated the frequency of promoter hypermethylation in invasive ductal breast cancers in the two races. Experimental Design: HIN-1, Twist, Cyclin D2, RAR-β, and RASSF1A were analyzed in DNA from 67 AA and 44 Cau invasive ductal breast cancers, stratified by age and estrogen receptor/progesterone receptor (ER/PR) status, by methylation-specific PCR. Hierarchical multiple logistic regression analysis was applied to determine estimated probabilities of methylation. Expression of HIN-1 mRNA was analyzed by in situ hybridization and quantitative reverse transcribed PCR. Results: Significant differences between races were observed in the ER−/PR−, age &amp;lt; 50 subgroup; AA tumors had higher frequency of methylation (P &amp;lt; 0.001) in four of five genes as compared with Cau and also a higher prevalence (80 versus 0%; P &amp;lt; 0.005) of three or more methylated genes per tumor. No differences in gene methylation patterns were observed across the two races for ER+/PR+ tumors in all ages and ER−/PR− tumors in age &amp;gt; 50. ER+/PR+ status was associated with higher frequency of methylation in Cau tumors of all ages but only with the age &amp;gt; 50 subgroup in AA. Frequent Cyclin D2 methylation was significantly associated (P = 0.01) with shorter survival time. Conclusion: ER−/PR−, age &amp;lt; 50 tumors in AA women, have a significantly higher frequency of hypermethylation than in those of Cau women. Comparative studies, such as these, could provide a molecular basis for differences in tumor progression and pathology seen in the two races.
Tumor Microsatellite-Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Colon Cancer
Authors: Christine M. Ribic, Daniel J. Sargent, Malcolm J. Moore, Stephen N. Thibodeau, Amy J. French, Richard M. Goldberg, Stanley R. Hamilton, Pierre Laurent-Puig, Robert Gryfe, Lois E. Shepherd, Dongsheng Tu, Mark Redston, Steven Gallinger
Journal: New England Journal of Medicine (2003)

Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors. We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer.
Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease
Authors: Jørgen Vestbo, Suzanne S. Hurd, Alvar G. Agustí, Paul W. Jones, Claus Vogelmeier, Antonio Anzueto, Peter J. Barnes, Leonardo M. Fabbri, Fernando J. Martinez, Masaharu Nishimura, Robert A. Stockley, Don D. Sin, Roberto Rodriguez-Roisin
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Section:ChooseTop of pageAbstract <<ContentsIntroduction1. Definition and Overvie...2. Diagnosis and Assessme...3. Therapeutic Options4. Management Of Stable C...5. Management of Exacerba...6. COPD and ComorbiditiesReferencesCITING ARTICLES
How to assess disease activity in patients with chronic urticaria?
Authors: A. Młynek, A. Zalewska‐Janowska, P. Martus, P. Staubach, T. Zuberbier, M. Maurer
Journal: Allergy (2008)

Background: The current EAACI/GA²LEN/EDF guidelines recommend assessing disease activity in chronic urticaria (CU) by using an established and well‐defined symptom score, i.e. the urticaria activity score (UAS), which combines daily wheal numbers and pruritus intensity. However, this UAS has never been formally tested for its suitability in assessing CU activity. Aim: To determine the UAS correlation with quality of life (QoL) in CU patients and to compare the UAS to other symptom scores. Methods: Chronic urticaria symptoms (wheals, erythema, angioedema, pruritus) were assessed on seven consecutive days in 111 CU patients for their numbers, duration, size, and/or intensity. Quality of life was assessed by using the Dermatology Life Quality Index. Both, urticaria activity and QoL were determined before and after a 3‐week period, in which the patients followed a pseudoallergen‐low diet. Results: Urticaria activity score values correlated positively, albeit weakly, with QoL impairment in CU patients ( r 2 = 0.31, P &lt; 0.05). Also, changes in QoL following a pseudoallergen‐low diet were reflected by the changes observed in the UAS ( r 2 = 0.30, P &lt; 0.05). No significant differences were found comparing the QoL correlation of the UAS and other symptom scores combining up to four CU symptom qualities. Quality of life correlation with UAS values increased with the number of days the UAS was assessed and plateaued starting from the fourth consecutive day. Conclusions: Our findings back the current guideline recommendations to use the UAS for monitoring disease activity in CU patients. Urticaria activity score mean values of at least four consecutive days should be used.
Health Effects of a Mixture of Indoor Air Volatile Organics, Their Ozone Oxidation Products, and Stress
Authors: Nancy Fiedler, Robert Laumbach, Kathie Kelly-McNeil, Paul Lioy, Zhi-Hua Fan, Junfeng Zhang, John Ottenweller, Pamela Ohman-Strickland, Howard Kipen
Journal: Environmental Health Perspectives (2005)

In our present study we tested the health effects among women of controlled exposures to volatile organic compounds (VOCs), with and without ozone (O3), and psychological stress. Each subject was exposed to the following three conditions at 1-week intervals (within-subject factor): VOCs (26 mg/m3), VOCs + O3 (26 mg/m3 + 40 ppb), and ambient air with a 1-min spike of VOCs (2.5 mg/m3). As a between-subjects factor, half the subjects were randomly assigned to perform a stressor. Subjects were 130 healthy women (mean age, 27.2 years; mean education, 15.2 years). Health effects measured before, during, and after each 140-min exposure included symptoms, neurobehavioral performance, salivary cortisol, and lung function. Mixing VOCs with O3 was shown to produce irritating compounds including aldehydes, hydrogen peroxide, organic acids, secondary organic aerosols, and ultrafine particles (particulate matter with aerodynamic diameter < 0.1 microm). Exposure to VOCs with and without O3 did not result in significant subjective or objective health effects. Psychological stress significantly increased salivary cortisol and symptoms of anxiety regardless of exposure condition. Neither lung function nor neurobehavioral performance was compromised by exposure to VOCs or VOCs + O3. Although numerous epidemiologic studies suggest that symptoms are significantly increased among workers in buildings with poor ventilation and mixtures of VOCs, our acute exposure study was not consistent with these epidemiologic findings. Stress appears to be a more significant factor than chemical exposures in affecting some of the health end points measured in our present study.
Macro- and Microstructural Magnetic Resonance Imaging Indices Associated With Diabetes Among Community-Dwelling Older Adults
Authors: Cherie M. Falvey, Caterina Rosano, Eleanor M. Simonsick, Tamara Harris, Elsa S. Strotmeyer, Suzanne Satterfield, Kristine Yaffe
Journal: Diabetes Care (2012)

OBJECTIVE To better understand the association between diabetes and cognitive impairment, we evaluated macro- and microstructural brain MRI measures for the total brain and regions of interest (ROIs) in a group of community-dwelling elders with and without diabetes. RESEARCH DESIGN AND METHODS MRI measures were obtained on 308 elders (mean age 83.3 years; n = 85 with diabetes) from the Health ABC Healthy Brain Substudy. We performed a series of linear regressions and used standardized β values to estimate the cross-sectional association between diabetes and macrostructural (gray matter volume [GMV] and white matter hyperintensities [WMHs]) and microstructural (mean diffusivity [MD] and fractional anisotropy [FA]) measures for the total brain and ROIs. Models were adjusted for age, race, and sex; GMV values for ROIs were also adjusted for total brain volume (TBV). RESULTS In multivariate-adjusted models, diabetes was associated with lower total GMV (P = 0.0006), GMV in the putamen (P = 0.02 for left and right), and TBV (P = 0.04) and greater cerebral atrophy (P = 0.02). There was no association with WMHs. On microstructural measures, diabetes was associated with reduced FA for total white matter (P = 0.006) and greater MD for the hippocampus (P = 0.006 left; P = 0.01 right), dorsolateral prefrontal cortex (P = 0.0007, left; P = 0.002, right), left posterior cingulate (P = 0.02), and right putamen (P = 0.02). Further adjustment for stroke, hypertension, and myocardial infarction produced similar results. CONCLUSIONS In this cross-sectional study, elders with diabetes compared with those without had greater brain atrophy and early signs of neurodegeneration. Further studies are needed to determine whether these structural changes associated with diabetes predict risk of cognitive decline.
Neonatal treatment with low doses of anti-idiotypic antibody leads to the expression of a silent clone.
Authors: J Hiernaux, C Bona, P J Baker
Journal: The Journal of Experimental Medicine (1981)

BALB/c mice immunized with bacterial levan (BL) produce an immune response that fails to generate antibody expressing the idiotype (Id) of the beta (2 leads to 6) fructosan-binding myeloma protein ABPC 48 (A48). Pretreatment of newborn BALB/c mice (at 1 d of age) with 0.01-10 microgram of affinity purified BALB/c anti-A48 Id antibody followed by immunization with BL 1-2 mo later produces an anti-BL response that expresses the A48 Id. This shows that A48 Id+ anti-BL clones belong to a normally silent fraction of the anti-BL repertoire. The activation of A48 Id+ anti-BL clones anti-A48 Id antibody is specific because the pretreatment of newborn mice with anti-MOPC 384 Id antibody, followed by immunization with BL, does not lead to its activation. Moreover, pretreatment of mice with anti-A48 Id antibody does not alter the MOPC 460 Id+ component of the anti-TNP response. It is also important to note that the activation of the A48 Id+ clone in pretreated mice requires subsequent immunization with BL.
Elevated Sarcoplasmic Reticulum Ca <sup>2+</sup> Leak in Intact Ventricular Myocytes From Rabbits in Heart Failure
Authors: Thomas R. Shannon, Steven M. Pogwizd, Donald M. Bers
Journal: Circulation Research (2003)

Altered sarcoplasmic reticulum (SR) Ca 2+ -ATPase and Na + -Ca 2+ exchange (NCX) function have been implicated in depressing SR Ca 2+ content and contractile function in heart failure (HF). Enhanced diastolic ryanodine receptor (RyR) leak could also lower SR Ca 2+ load in HF, but direct cellular measurements are lacking. In this study, we measure SR Ca 2+ leak directly in intact isolated rabbit ventricular myocytes from a well-developed nonischemic HF model. Abrupt block of SR Ca 2+ leak by tetracaine shifts Ca 2+ from the cytosol to SR. The tetracaine-induced decline in [Ca 2+ ] i and increase total SR Ca 2+ load ([Ca 2+ ] SRT ) directly indicate the SR Ca 2+ leak (before tetracaine). Diastolic SR Ca 2+ leak increases with [Ca 2+ ] SRT , and for any [Ca 2+ ] SRT is greater in HF versus control. Mathematical modeling was used to compare the relative impact of alterations in SR Ca 2+ leak, SR Ca 2+ -ATPase, and Na + -Ca 2+ exchange on SR Ca 2+ load in HF. We conclude that increased diastolic SR Ca 2+ leak in HF may contribute to reductions in SR Ca 2+ content, but changes in NCX in this HF model have more impact on [Ca 2+ ] SRT .
Patterns of Capillary Plasma Perfusion in Brains of Conscious Rats During Normocapnia and Hypercapnia
Authors: Roger Abounader, Johannes Vogel, Wolfgang Kuschinsky
Journal: Circulation Research (1995)

The present study aimed to investigate the distribution pattern of plasma flow velocities in brain capillaries. We tested the hypothesis that plasma flow velocities are heterogeneous in the brain capillaries of normocapnic conscious rats and become more homogeneous during increased cerebral blood flow induced by hypercapnia. We developed a method that makes it possible to detect the distribution pattern of plasma flow velocities from the intravascular dye concentrations measured in different capillaries. Evans blue was injected intravenously as a bolus, and 3 to 4 seconds later the rats were decapitated. During this period, a steep increase in arterial dye concentration was verified by frequent arterial blood sampling. Under such conditions, divergent plasma flow velocities in different capillaries yield unequal intravascular dye concentrations. Dye concentrations were measured in several hundred capillaries of brain cryosections using quantitative fluorescence microscopy based on calibration curves obtained from anesthetized rats. The results show a high degree of variation in the intravascular dye concentration during normocapnia. During increasing stages of hypercapnia, the variation was gradually reduced. The coefficient of variation (SD/mean-100) of intracapillary dye concentration decreased from 76% at normocapnia to 22% at extreme hypercapnia (PCO2 of 87 mm Hg), thus showing an inverse correlation with arterial PCO2 (r = .97). The heterogeneity of intravascular dye concentrations observed in the present experiments indicates heterogeneous velocities of plasma perfusion in different brain capillaries during normocapnia and a more homogeneous distribution pattern during hypercapnic hyperemia.
Cellular Responses to the Major Allergen of Olea Europaea in Subjects with Local and Systemic Allergic Rhinitis
Authors: Paloma Campo, Mayte Villalba, Carmen Rondon, Esther Barrionuevo Sanchez, Luisa Galindo, J.C. Lopez-Rodriguez, Maria J. Torres, Miguel Blanca, Cristobalina Mayorga
Journal: Journal of Allergy and Clinical Immunology (2015)