tbuckley/cabot-search huggingface dataset:
617. A Synthetic Promoter Drives Macrophage Expression of ApoE and Ameliorates Atherosclerosis
Authors: Senlin Li, Weijing He, Mei Qiang, Robert A. Reddick, Gregory L. Freeman
Journal: Molecular Therapy (2005)

Macrophages, derived from hematopoietic stem cells (HSC), play a key role in atherosclerosis. To treat atherosclerosis, we plan to alter expression of relevant genes in macrophages by ex vivo transduction of HSC with lentiviral vectors carrying a macrophage-specific promoter. Myeloid promoter cis-elements were randomly ligated and the resultant DNA inserted into a reporter vector upstream of a myeloid basal promoter. Luciferase activity of some synthetic promoters was 10-200-fold over that of the CSF1R macrophage promoter in Thp-1 and other macrophage cell lines, but quite low in non-macrophage cells compared with the CMV promoter. Mouse bone marrow was collected, transduced ex vivo with lentiviral vectors expressing GFP driven either by a synthetic promoter (SP-GFP) or CMV promoter (CMV-GFP), and transplanted into lethally irradiated recipients. At various time points (1.5, 4, 8, 11, 15 months) post-transplant, peripheral blood analyzed by FACS and GFP expression was quite stable over time. SP-GFP expression was detected in most CD11b+ leukocytes, but only in a small fraction of CD11b- cells and not at all in erythrocytes, while CMV-GFP expression was observed ubiquitously. To test the promoters in macrophage gene therapy for atherosclerosis, we transduced apoE-/- BM cells with a lentiviral vector encoding human apoE (apoE) and transplanted them into apoE-/- mice. Comparable levels of apoE were measured in culture media of peritoneal macrophages from either SP-apoE or CMV-apoE recipient mice. However, serum apoE of SP-apoE recipients was only one fourth of that of CMV-apoE, implying that SP activity was restricted to the monocyte/macrophage lineage. Macrophage expression of apoE from 10 to 26 weeks of age significantly reduced atherosclerotic lesions in recipient mice. In conclusion, the combination of the synthetic macrophage promoter, lentiviral vectors, and bone marrow stem cell transplantation ameliorates atherogenesis and leads to a novel treatment of this disease.
The Complement Response Against an Oncolytic Virus Is Species-Specific in Its Activation Pathways
Authors: Hiroaki Wakimoto, Keiro Ikeda, Tatsuya Abe, Tomotsugu Ichikawa, Fred H Hochberg, R.Alan B Ezekowitz, Mark S Pasternack, E.Antonio Chiocca
Journal: Molecular Therapy (2002)

A variety of oncolytic viruses (OVs) are being tested in clinical trials for different human cancers. Although the innate immune response is critical as the first line of defense in thwarting viral infection of mammalian cells, little is known of this response in the context of OV therapy of tumors. Investigations of activities against a herpes simplex OV demonstrated that HSV-seronegative sera from rats, mice, and humans efficiently neutralize this OV in vitro. Although this neutralization is due to complement, activation of this innate host defense differs in its pathways among species routinely used in preclinical tumor trials. In rats, both natural immunoglobulins and mannan-binding lectin (MBL) activate complement against the OV, while in mice only MBL is relevant to this activation. However, in humans only natural immunoglobulins play a role in complement activity. Quantitative analyses confirm that in vivo complement depletion facilitates the initial infection of tumors by systemic OVs. Therefore, complement activation against oncolytic HSV vectors proceeds through different pathways in different species. These findings are relevant to preclinical rodent studies of OV therapy and their application to human clinical trials.
Effects of Oral Erythromycin on Fasting and Postprandial Antroduodenal Motility in Patients With Type I Diabetes, Measured With an Ambulatory Manometric Technique
Authors: Melvin Samsom, Rik J A Jebbink, Louis M A Akkermans, B Bravenboer, Gerard P Van Berge-Henegouwen, Andre J P M Smout
Journal: Diabetes Care (1997)

The aim of this double-blind crossover study was to evaluate the effects of oral erythromycin (250 mg t.i.d.) on fasting and postprandial gastrointestinal motility and gastrointestinal symptoms in patients with type I diabetes.Antroduodenal motility was recorded with an ambulatory manometric technique for a 20-h period, including a high-caloric high-fat dinner and a low-caloric low-fat breakfast and a long fasting period, after 2 weeks erythromycin and placebo treatment in 12 patients with type I diabetes. During the manometric study, plasma glucose concentrations were assessed by frequent self-testing. Gastrointestinal symptoms were scored daily to assess the severity of the symptoms (range 0-3).Oral erythromycin decreased the migrating motor complex cycle length from 118.9 +/- 46.0 to 86.2 +/- 25.3 min (P = 0.03) by shortening phase II from 68.7 +/- 23.5 to 48.5 +/- 19.4 min (P < 0.05). The total number of duodenal phase III increased from 48 to 62 (P = 0.075). However, the degree of antral participation to duodenal phase III did not increase. Erythromycin significantly decreased the duration of the postprandial period after dinner (from 417.0 +/- 137.9 to 348.8 +/- 93.8 min, P = 0.04). During this shorter postprandial period, the number of antral contractions (P < 0.01) and the antral motility index increased (P < 0.03), and early phase III activity at the level of the duodenum was abolished. In diabetic patients with antral hypomotility, after dinner, the mean symptom score improved significantly, from 2.07 +/- 0.86 to 1.52 +/- 0.63 (P = 0.018).This ambulatory antroduodenal manometric study showed that oral erythromycin (250 mg t.i.d.) improves both fasting and postprandial antroduodenal motor activity after a high-caloric meal in patients with type I diabetes. Furthermore, in diabetic subjects with postprandial antral hypomotility, erythromycin reduces dyspeptic symptoms.
Nodular Pneumonitis after Cancer Chemotherapy
Authors: James A. Talcott
Journal: Annals of Internal Medicine (1989)

Letters and Corrections1 January 1989Nodular Pneumonitis after Cancer ChemotherapyJames A. Talcott, MD, Marc B. Garnick, MD, Paul C. Stomper, MD, John J. Godleski, MD, Jerome P. Richie, MDJames A. Talcott, MDSearch for more papers by this author, Marc B. Garnick, MDSearch for more papers by this author, Paul C. Stomper, MDSearch for more papers by this author, John J. Godleski, MDSearch for more papers by this author, Jerome P. Richie, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-110-1-91_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:Trump and colleagues (1) reported the frequency of benign radiographic nodules and infiltrates at the lung bases of young men with testis cancer treated with combination chemotherapy, a finding consistent with the experience of other researchers (2-4). We have recently reported a case of advanced non-seminomatous testis cancer in a 56-year-old patient who developed multiple nodular and cavitary radiographic lesions in the upper lobes after similar therapy with cisplatin, vinblastine, and bleomycin (5). Lung biopsy showed multiple granulomata with multinucleated giant cells, without microbiologic or pathologic evidence of infectious agents or tumor. The advanced age of the...References1. TrumpBartelPozniak DEM. Nodular pneumonitis after chemotherapy for germ cell tumors. Ann Intern Med. 1988;109:431-2. LinkGoogle Scholar2. MayrBauerClemmHartenstein VWCR. Problems in the differentiation of lung infiltrates following bleomycin therapy from metastases. ROFO. 1984;141:409-14. CrossrefMedlineGoogle Scholar3. GlasierSiegel CM. Multiple pulmonary nodules: unusual manifestation of bleomycin toxicity. AJR. 1981;137:155-6. CrossrefMedlineGoogle Scholar4. NachmanBaumWhiteCruissi JEHF. Bleomycin-induced pulmonary fibrosis mimicking recurrent metastatic disease in a patient with testicular carcinoma: case report of the CT scan appearance. Cancer. 1981;47:236-9. CrossrefMedlineGoogle Scholar5. TalcottGarnickStomperGodleskiRichie JMPJJ. Cavitary lung nodules associated with combination chemotherapy containing bleomycin. J Urol. 1987;138:619-20. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Dana-Farber Cancer Institute Brigham and Women's Hospital Boston, MA 02115 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1989Volume 110, Issue 1Page: 91-91KeywordsBiopsyCancer chemotherapyCombination chemotherapyGiant cellsLesionsLung and intrathoracic tumorsLungsPneumonitisTesticular cancer Issue Published: 1 January 1989 PDF DownloadLoading ...
High Levels of Dopamine Activity in the Basal Ganglia of Cigarette Smokers
Authors: Raimo K.R. Salokangas, Harry Vilkman, Tuula Ilonen, Tero Taiminen, Jï¿½n Bergman, Merja Haaparanta, Olof Solin, Anu Alanen, Erkka Syvã«¡hti, Jarmo Hietala
Journal: American Journal of Psychiatry (2000)

The authors' goal was to study presynaptic dopamine activity in smoking and nonsmoking human subjects in vivo.[(18)F]Fluorodopa ([(18)F]DOPA) uptake K(i) values in the basal ganglia of nine smoking and 10 nonsmoking healthy men were measured with positron emission tomography.Significantly higher [(18)F]DOPA uptake was observed in both the putamen (average 17.3% higher) and the caudate (average 30.4% higher) of smokers than in those of nonsmokers.Smoking is related to greater dopamine activity in the human basal ganglia. Nicotine-induced dopamine activity may be a relevant mechanism in dependence on cigarette smoking.
Kiwifruit allergy across Europe: Clinical manifestation and IgE recognition patterns to kiwifruit allergens
Authors: Thuy-My Le, Merima Bublin, Heimo Breiteneder, Montserrat Fernández-Rivas, Riccardo Asero, Barbara Ballmer-Weber, Laura Barreales, Peter Bures, Simona Belohlavkova, Frédéric de Blay, Michael Clausen, Ruta Dubakiene, David Gislason, Els van Hoffen, Monika Jedrzejczak-Czechowicz, Marek L. Kowalski, Tanya Kralimarkova, Jonas Lidholm, Åsa Marknell DeWitt, Clare E.N. Mills, Nikolaos G. Papadopoulos, Todor Popov, Ashok Purohit, Ronald van Ree, Suranjith Seneviratne, Athanasios Sinaniotis, Colin Summers, Sonia Vázquez-Cortés, Stefan Vieths, Lothar Vogel, Karin Hoffmann-Sommergruber, André C. Knulst
Journal: Journal of Allergy and Clinical Immunology (2012)
Treatment of shingles and post-herpetic neuralgia
Authors: P. Todd, J. Thomson
Journal: BMJ (1989)

from studies of women taking unopposed oestro- gens.rhe question of progestogens is complex and unresolved, as can be seen by the supplement of Fertility and Sterility that was devoted to such topics.'To date there is information only concern- ing effects on lipids and carbohydrate metabolism but not in any strong sense related to atheroma or clinical disease.Nevertheless, there are grounds for applying pressure on manufacturers to use smaller doses of progestogens: duration rather than quantity seems the important factor in terms of protection against endometrial cancer, and indeed this seems to be the tendency with some newer preparations.Nevertheless, I support the quest for compounds with lower binding affinity for androgen receptor.The subject is rapidly moving and I feel that menopausal patients can safely be given favourable advice about the benefits of hormone replacement treatment, but we should be prepared to make changes in treatment in the light of developments.
USE OF BETA-BLOCKERS AND REDUCTION IN ALL-CAUSE MORTALITY IN HOSPITALIZED MEDICARE BENEFICIARIES WITH ACUTE DIASTOLIC HEART FAILURE: A PROPENSITY-MATCHED STUDY OF THE OPTIMIZE-HF
Authors: Ali Ahmed, Yan Zhang, Marjan Mujib, Tarun Arora, Margaret Feller, Meredith Kilgore, Inmaculada Aban, Thomas Love, Richard Allman, Gregg Fonarow
Journal: Journal of the American College of Cardiology (2011)
44 A multi-gene signature accurately predicts the risk of bridging fibrosis/cirrhosis in patients with chronic hepatitis C
Authors: H. Huang, T.L. Wright, R.C. Cheung, T.J. Layden, S. Friedman, N. Bzowej, C. Cooper, A. Jacobson, R. Venkatesh, O.T. Abar, J. Chan, J.J. Catanese, D.U. Leong, L. Yee, T.J. White, J.J. Sninsky, M. Shiffman
Journal: Journal of Hepatology (2006)
QUANTITATIVE INTERPRETATION OF MYOCARDIAL T1???201 SINGLEPHOTON EMISSION COMPUTERIZED TOMOGRAMS
Authors: J Maddahi, F Prigent, H Staniloff, E Garcia, A Becerra, K Van Train, HJC Swan, A Waxman, D Berman
Journal: Clinical Nuclear Medicine (1984)

Probabilistic criteria for abnormality would enhance application of stress-redistribution Tl-201 rotational tomography (tomo) for evaluation of coronary artery disease (CAD). Thus, 75 pts were studied, of whom 35 had angiographic CAD (≥50% coronary narrowing) and 40 were normal (nl). 0.6 cm thick oblique and sagittal tomos were obtained on all pts. On each tomo, 60 equidistant count samples were automatically obtained resulting in 273 to 764 total myocardial sample points. Each point's activity was then compared by computer to previously established corresponding mean nl values. Defect extent (E) represented % of myocardial points having a count value less than nl, and defect severity (S) was defined as the sum of the deviation of all abnl points from nl. Logistic regression analysis was done on a random sample of 38 pts (23 nls and 18 with CAD) to assess the likelihood of CAD as a function of E and S of tomographic perfusion defect. Likelihood of CAD =e,k/1+ek, where k=1.01+ 1.49S–0.208E. The validity of this model was prospectively tested in the remaining 37 pts (20 nls and 17 with CAD) by comparing the predicted and observed likelihood of CAD in four subgroups (I–IV). No significant difference (p=.1) was found between predicted and observed likelihood of CAD. I II III IV Predicted 1.9% 11% 32% 98% Observed 1.1% (1/9) 33% (3/9) 44% (4/9) 89% (9/10) Thus, a logistic model has been developed and validated that assigns a coronary disease likelihood to the quantified tomographic size of myocardial perfusion defects.
Expression of p53 and Prognosis in Children with Malignant Gliomas
Authors: Ian F. Pollack, Sydney D. Finkelstein, Jeffrey Woods, Judith Burnham, Emiko J. Holmes, Ronald L. Hamilton, Allan J. Yates, James M. Boyett, Jonathan L. Finlay, Richard Sposto
Journal: New England Journal of Medicine (2002)

The prognosis of children with high-grade gliomas is uncertain, even when clinical and histologic findings are considered. We investigated whether mutations in the TP53 gene or the degree of expression of p53 protein in high-grade gliomas is associated with progression-free survival in children with these tumors.
Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation
Authors: Hyeyoung Kim, Nam-Joon Yi, Juyeun Lee, Joohyun Kim, Mi-Ra Moon, Jaehong Jeong, Jeong-Moo Lee, Tae Suk You, Suk-Won Suh, Min-Su Park, YoungRok Choi, Geun Hong, Hae Won Lee, Kwang-Woong Lee, Kyung-Suk Suh
Journal: Clinical and Molecular Hepatology (2014)

Background/Aims The dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT). Methods Two sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT. Results In the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively. Conclusions A reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT. Keywords: Area under the curve; Mycophenolate mofeti; Mycophenolic acid; Therapeutic drug monitoring; Liver transplant
799-3 Left Ventricular Function and Immunohistological Findings in Patients with Dilated Cardiomyopathy: A Follow-up Study
Authors: Igor Janda, Mira C. Schannwell, Otto N. Krogmann, Uwe Kühl, Heinz P. Schultheiss, Bodo E. Strauer
Journal: Journal of the American College of Cardiology (1995)
Effects of PCB exposure on neuropsychological function in children.
Authors: Susan L Schantz, John J Widholm, Deborah C Rice
Journal: Environmental Health Perspectives (2003)

In the last decade advances in the analytic methods for quantification of polychlorinated biphenyls (PCBs) have resulted in widespread availability of congener-specific analysis procedures, and large amounts of data on PCB congener profiles in soil, air, water, sediments, foodstuffs, and human tissues have become available. These data have revealed that the PCB residues in environmental media and human tissues may not closely resemble any of the commercial PCB mixtures, depending on source of exposure, bioaccumulation through the food chain, and weathering of PCBs in the environment. At the same time, toxicological research has led to a growing awareness that different classes of PCB congeners have different profiles of toxicity. These advances in analytic techniques and toxicological knowledge are beginning to influence the risk assessment process. As the data from ongoing PCB studies assessing the mediators of neurobehavioral outcomes in children are published, the weight of evidence for PCB effects on neurodevelopment is growing. Studies in Taiwan, Michigan (USA), New York (USA), Holland, Germany, and the Faroe Islands have all reported negative associations between prenatal PCB exposure and measures of cognitive functioning in infancy or childhood. The German study also reported a negative association between postnatal PCB exposure and cognitive function in early childhood--a result that had not been found in previous studies. Only one published study in North Carolina (USA) has failed to find an association between PCB exposure and cognitive outcomes. Despite the fact that several more recent studies have used congener-specific analytic techniques, there have been only limited attempts to assess the role of specific PCB congeners or classes of congeners in mediating neurodevelopmental outcomes. From a statistical standpoint, attempts to determine the role of individual congeners in mediating outcomes are hampered by the fact that concentrations of most individual congeners are highly correlated with each other and with total PCBs. From a toxicological standpoint, these efforts are hampered by the fact that many of the PCB congeners present in human tissues have never been studied in the laboratory, and their relative potency to produce nervous system effects is unknown. More complete information on the health effects of various congeners or congener classes would allow more informed scientific and risk assessment decisions.
Inhibition of rat vascular smooth muscle proliferation in vitro and in vivo by bone morphogenetic protein-2.
Authors: T Nakaoka, K Gonda, T Ogita, Y Otawara-Hamamoto, F Okabe, Y Kira, K Harii, K Miyazono, Y Takuwa, T Fujita
Journal: Journal of Clinical Investigation (1997)

Vascular proliferative disorders are characterized by the proliferation of vascular smooth muscle cells (SMCs) and excessive extracellular matrix synthesis. We found that bone morphogenetic protein-2 (BMP-2) inhibited serum-stimulated increases in DNA synthesis and cell number of cultured rat arterial SMCs in a fashion quite different from that in the case of transforming growth factor-beta1 (TGF-beta1). In addition, TGF-beta1 stimulated collagen synthesis in SMCs, whereas BMP-2 did not. In an in vivo rat carotid artery balloon injury model, the adenovirus-mediated transfer of the BMP-2 gene inhibited injury-induced intimal hyperplasia. These results indicate that BMP-2 has the ability to inhibit SMC proliferation without stimulating extracellular matrix synthesis, and suggest the possibility of therapeutic application of BMP-2 for the prevention of vascular proliferative disorders.
THE TYPES OF PNEUMOCOCCI IN TUBERCULOUS SPUTUM
Authors: Harold W. Lyall
Journal: The Journal of Experimental Medicine (1915)

The success of Cole 1 and his associates 2 in establishing four groups among the pneumococci affords a new basis for the study of the transmissibility and pathology of acute lobar pneumonia. The most important result of this work is, perhaps, its bearing on the epidemiology of the disease. It has been generally accepted that the pneumococci of the normal mouth may, under favorable conditions, become implanted in the lung and are there able to set up the condition known as lobar pneumonia. The work of Rosenow 3 has been considered as favoring this theory by supposing that the pneumococci of the mouth, under changed environmental conditions, undergo a mutation into a virulent type. On the other hand, the work indicating that different types of pneumococci may operate in producing pneumonia, raises the question as to whether pneumonia may not be a transmissible or epidemic disease caused by distinct, virulent types of this organism, passed from individual to individual. To prove the first theory, it must be shown either that the organism of acute pneumonia and that ordinarily present in the healthy mouth are the same, or, postulating a mutation, that the comparatively avirulent mouth strain, as a result of the changed lung condition, assumes the characteristics of one of the virulent groups associated with the acute disease. It was with this problem in mind that the present work was undertaken. In pulmonary tuberculosis and the other lung conditions
MORPHIN AND COCAIN INTOXICATION.
Authors: GEORGE P. DALE
Journal: JAMA (1903)

A few years ago I had occasion to observe that the prevalence of the several drug habits, notably morphin and cooain, was on the increase, especially among that class of people found in the charity wards of the public hospitals. The victim of one or the other of these drugs becomes such after a somewhat different path. Cocainism is more quickly acquired, cases being on record of cocain eaters in Calcutta who have raised their dose from 1 to 12 grains in a month's time. This, while it is exceptional in this country, is frequent in India and other tropical countries, where the habit is very prevalent. The doses may be enormously increased, and 30 to 40 grains a day is not uncommon. The habit is on the increase, the drug often being given by physicians as a cure for morphinism, and is also greatly used for its sustaining virtues