tbuckley/cabot-search huggingface dataset:
In Vivo Gene Transfer of Nitric Oxide Synthase Enhances Vasomotor Function in Carotid Arteries From Normal and Cholesterol-Fed Rabbits
Authors: Keith M. Channon, HuSheng Qian, Valentina Neplioueva, Michael A. Blazing, Ercument Olmez, Geetha A. Shetty, Scot A. Youngblood, John Pawloski, Timothy McMahon, Jonathan S. Stamler, Samuel E. George
Journal: Circulation (1998)

Background —The vascular endothelium is anatomically intact but functionally abnormal in preatherosclerotic states, and an early deficit in the bioavailability of nitric oxide (NO) or related molecules has been described in both humans and animal models. We hypothesized that the targeted gene transfer of NO synthase (NOS) isoforms might ameliorate or reverse the deficit. Methods and Results —We constructed a recombinant adenovirus, Ad.nNOS, that expresses the neuronal isoform of NOS (nNOS) and used it for in vivo endovascular gene transfer to carotid arteries (CA) from normal and cholesterol-fed rabbits. Vessels were harvested 3 days after gene transfer. In CA from normal rabbits, Ad.nNOS generated high levels of functional nNOS protein predominantly in endothelial cells and increased vascular NOS activity by 3.4-fold relative to sham-infected control CA. Ad.nNOS gene transfer also significantly enhanced endothelium-dependent vascular relaxation to acetylcholine; at 3 μmol/L acetylcholine, Ad.nNOS-treated arteries showed an 86±4% reduction in precontracted tension, whereas control CA showed a 47±6% reduction in tension. Contraction in response to phenylephrine and relaxation in response to nitroprusside were unaffected in both control and Ad.nNOS-treated CA. To determine the effect of Ad.nNOS in atherosclerotic arteries, 10 male New Zealand White rabbits maintained on a 1% cholesterol diet for 10 to 12 weeks underwent gene transfer according to the same protocol used in normal rabbits. Ad.nNOS-treated arteries showed a 2-fold increase in NADPH-diaphorase staining intensity relative to sham-infected and Ad.βGal-treated arteries. The CA from cholesterol-fed rabbits showed impaired acetylcholine-induced relaxation, but this abnormality was almost entirely corrected by Ad.nNOS gene transfer. Conclusions —In vivo adenovirus-mediated endovascular delivery of nNOS markedly enhances vascular NOS activity and can favorably influence endothelial physiology in the intact and atherosclerotic vessel wall.
The clinical features of drug-induced liver injury observed through liver biopsy: focus on relevancy to autoimmune hepatitis
Authors: Hye Young Ju, Jae Young Jang, Soung Won Jeong, Sung Ae Woo, Min Gyu Kong, Hee Yoon Jang, Sae Hwan Lee, Sang Gyune Kim, Sang-Woo Cha, Young Seok Kim, Young Deok Cho, So Young Jin, Hong Soo Kim, Boo Sung Kim
Journal: Clinical and Molecular Hepatology (2012)

Accurate diagnosis of drug-induced liver injury (DILI) is difficult without considering the possibility of underlying diseases, especially autoimmune hepatitis (AIH). We investigated the clinical patterns in patients with a history of medication, liver-function abnormalities, and in whom liver biopsy was conducted, focusing on accompaniment by AIH.The clinical, serologic, and histologic findings of 29 patients were compared and analyzed. The patients were aged 46.2±12.8 years (mean±SD), and 72.4% of patient were female. The most common symptom and causal drug were jaundice (58.6%) and herbal medications (55.2%), respectively.Aspartate aminotransferase (AST), alanine aminotransferase, total bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase levels were 662.2±574.8 U/L, 905.4±794.9 U/L, 12.9±10.8 mg/dL, 195.8±123.3 U/L, and 255.3±280.8 U/L, respectively. According to serologic and histologic findings, 21 cases were diagnosed with DILI and 8 with AIH. The AIH group exhibited significantly higher AST levels (537.1±519.1 vs. 1043.3±600.5 U/L), globulin levels (2.7±0.4 vs. 3.3±0.5 g/dL), and prothrombin time (12.9±2.4 vs. 15.2±3.9 s; P<0.05). Antinuclear antibody was positive in 7 of 21 cases of DILI and all 8 cases of AIH (P=0.002). The simplified AIH score was 3.7±0.9 in the DILI group and 6.5±0.9 in the AIH group (P<0.001).Accurate diagnosis is necessary for patients with a history of medication and visits for liver-function abnormalities; in particular, the possibility of AIH should be considered.
Assessment of Coronary Stenosis Severity and Transmural Perfusion Gradient by Myocardial Contrast Echocardiography
Authors: Hisashi Masugata, Bruno Cotter, Barry Peters, Koji Ohmori, Katsufumi Mizushige, Anthony N. DeMaria
Journal: Circulation (2000)

Background —The present study (1) compared the ability of power Doppler imaging with that of gray-scale B-mode tissue imaging to opacify the myocardium and detect coronary stenosis by myocardial contrast echocardiography and (2) compared the response of video intensity (VI) to variable pulsing intervals for each modality. Methods and Results —Four grades of left anterior descending coronary artery (LAD) stenoses were created in 9 open-chest dogs. Stenoses reduced resting LAD flow by 25%, 50%, 75%, and 100% of baseline by flow probe. Myocardial contrast echocardiography was performed during varying ECG gated pulsing intervals (PIs) from 1:1 to 1:10. By gray-scale imaging, background-subtracted LAD bed VI was less than baseline VI at all PIs for the 100% reduced-flow state but not for any other flow state or interval. By power Doppler imaging, LAD bed VI was less than baseline VI at all intervals for 75% and 100% reduced-flow states but only 1:1 and 1:2 for 25% and 50% reduced-flow states, respectively. Correlation of VI and myocardial blood flow (determined by use of fluorescent microspheres) ratios from stenosed versus normal beds was stronger by power Doppler imaging. A transmural opacification gradient with stenosis was visualized and measured by power Doppler imaging, but it was insignificant by gray-scale imaging. The ratio of endocardial/epicardial flow determined by use of fluorescent microspheres was correlated with VI by power Doppler imaging at all PIs. Conclusions —Power Doppler imaging has advantages compared with gray-scale imaging in opacifying the myocardium and in detecting coronary stenosis and altered transmural distribution of myocardial perfusion from peak VI. Because VI differences from baseline at long PI vary for mild versus severe (75% and 100%, respectively) reduced-flow states, power Doppler imaging may provide a method to quantify coronary stenoses.
FABRY'S DISEASE IN CHILDREN
Authors: W. P. GROOT
Journal: British Journal of Dermatology (1970)

Journal Article FABRY'S DISEASE IN CHILDREN Get access W. P. de GROOT W. P. de GROOT Binnengasthuis, University of Amsterdam, Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue 4, 1 April 1970, Pages 329–332, https://doi.org/10.1111/j.1365-2133.1970.tb06828.x Published: 01 April 1970 Article history Accepted: 29 September 1969 Published: 01 April 1970
Differences in development of coronary arteries and veins
Authors: M Vrancken Peeters
Journal: Cardiovascular Research (1997)

Objective: The differentiation of the coronary vasculature was studied to establish in particular the formation of the coronary venous system. Methods: Antibody markers were used to demonstrate endothelial, smooth muscle, and fibroblastic cells in serial sections of embryonic quail hearts. The anti-β myosin heavy chain and the neuronal marker HNK-1 were added to our incubation protocol. Results: In HH32, the coronary vascular network has developed into a circulatory system with connections to the sinus venosus, the aorta and the right atrium. The connections between the aorta and the right atrium allow for direct arteriovenous shunting. Subsequently, differentiation into coronary arteries and veins occurs with an interposed capillary network. The smooth muscle cells of the coronary arterial media derive from the subepicardial layer, whereas the subepicardially located cardiac veins recrute atrial myocardium, as these cells express the β-myosin heavy chain antigen. Ganglia are located in the subepicardium close to the vessels, while nerve fibres tend to colocalize with the formed vessel channels. Conclusions: A new finding is presented in which the subepicardial coronary veins have a media that consists of myocardial cells. The close positional relationship of neural tissue and coronary vessels that penetrate the heart wall is explained as inductive for vessel wall differentiation, but not for invasion into the heart.
Generic Consent for Genetic Screening
Authors: S Elias, G J Annas
Journal: New England Journal of Medicine (1994)

Our ability to translate our expanding genetic knowledge into usable information for individual men and women is at best uncertain. Today many adults are offered genetic counseling to help them make reproductive decisions, either before they attempt to achieve a pregnancy or to help them decide whether to continue or terminate one. Taking a family history and, when indicated, recommending certain tests to identify carriers of genetic diseases are standard in obstetrical care. Today's screening tests usually focus on conditions that occur either in the family or in the racial or ethnic group of one or both prospective parents. As . . .
Detection of anabolic steroids by radioimmunoassay.
Authors: R. V. Brooks, R. G. Firth, N. A. Sumner
Journal: British Journal of Sports Medicine (1975)

The synthetic anabolic steroids have structural features which distinguish them from the natural steroid hor- mones.It should therefore be possible to detect the taking of these substances by testing for their presence in either blood or urine.At present suitable techniques
Advances in the Treatment of Prostate Cancer
Authors: Mark Pomerantz, Philip Kantoff
Journal: Annual Review of Medicine (2006)

Several recent advances have been made in the management of prostate cancer. Active surveillance is an increasingly attractive and reasonable approach for those with low-volume, low-risk disease. For locally advanced or localized high-risk disease, neoadjuvant and adjuvant therapies are emerging as the standard of care. Innovative uses of traditional hormonal treatments can potentially limit common side effects. Recent data also support the utility of second-line hormonal therapy. For the first time, a survival advantage with the use of chemotherapy has been established. Much work is under way to augment its efficacy with novel agents such as targeted therapeutics and tumor vaccines. Recent scientific breakthroughs suggest additional strategies in treating prostate cancer.
Activity of a Novel bcl-2/bcl-xL-Bispecific Antisense Oligonucleotide Against Tumors of Diverse Histologic Origins
Authors: O Gautschi, S Tschopp, R A Olie, S H Leech, A P Simões-Wüst, A Ziegler, B Baumann, B Odermatt, J Hall, R A Stahel, U Zangemeister-Wittke
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Increased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL is involved in the development and progression of many tumors. We recently reported that the bcl-2/bcl-xL-bispecific antisense oligonucleotide 4625 induces apoptosis in lung carcinoma cells. To further assess the therapeutic potential of oligonucleotide 4625, we investigated its effect on a series of human tumor cell lines of diverse histologic origins in vitro and in vivo. Methods: Oligonucleotide 4625-mediated inhibition of bcl-2 and bcl-xL expression in vitro was measured in breast carcinoma cells with the use of reverse transcription–polymerase chain reaction (PCR), real-time PCR, and western blotting. Cytotoxicity was assessed in several different cell lines by measurement of tumor cell growth, propidium iodide uptake, and nuclear apoptosis. The in vivo activity of oligonucleotide 4625 was determined by the inhibition of growth of established tumor xenografts in nude mice, immunohistochemical staining of Bcl-2 and Bcl-x proteins in the tumors, and western blotting of tumor lysates. Apoptosis in tumor xenografts was detected with the use of in situ TUNEL (i.e., terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling) staining. All statistical tests are two-sided. Results: In breast carcinoma cells, oligonucleotide 4625 treatment reduced bcl-2 and bcl-xL messenger RNA levels in a dose-dependent manner. At 600 nM, oligonucleotide 4625 reduced Bcl-2 and Bcl-xL protein levels to 25% (95% confidence interval [CI] = 16% to 34%) and 20% (95% CI = 14% to 26%), respectively, of the levels in untreated cells and it decreased viability in all cell lines mainly by inducing apoptosis. In vivo, oligonucleotide 4625 statistically significantly inhibited the growth of breast and colorectal carcinoma xenografts by 51% (95% CI = 28% to 74%) and 59% (95% CI = 44% to 74%), respectively, relative to those treated with control oligonucleotide 4626; it also reduced Bcl-2 and Bcl-xL protein levels and induced tumor cell apoptosis. Conclusion: The bcl-2/bcl-xL-bispecific antisense oligonucleotide 4625 merits further study as a novel compound for cancer therapy.
Intervention trials and ventilation distribution in mild cystic fibrosis lung disease: will it all come out in the wash?
Authors: G.L. Hall, J. Stocks
Journal: European Respiratory Journal (2011)

The identification of clinically relevant end-points for use in clinical trials of new treatments in cystic fibrosis (CF) lung disease is an ongoing problem for physicians and researchers working in the field of CF care. Lung disease almost certainly starts in early infancy 1–6 and is progressive, leading to significant structural lung disease in the preschool years 7. Despite this, the majority of young children with CF tend to have spirometry within the normal range at early school age 1, 8, 9. It is well recognised that relying on spirometry alone to identify children at risk of progressive lung disease has significant limitations. This has led to renewed emphasis on the assessment of physiological outcomes in infancy and the preschool years, as well as increased focus on lung function tests that are more sensitive to early lung dysfunction than spirometry 10–13.

One such outcome is the assessment of ventilation inhomogeneity obtained from the multiple breath inert gas washout test (MBW), the most commonly reported outcome being the lung clearance index (LCI). A significant advantage of this technique is that it can be applied from infancy through to adulthood, with only minor changes in equipment and methodology, particularly from the preschool years onwards 14–16. The LCI has been shown to be abnormal in the presence of normal spirometry in both preschool children 7 and older children with CF 9, 17–22, suggesting that it is a more sensitive marker of early lung disease in such …
Managing Menopausal Symptoms in Breast Cancer Survivors: Results of a Randomized Controlled Trial
Authors: P. A. Ganz
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Menopausal symptoms (e.g., hot flashes, vaginal dryness, and stress urinary incontinence) are very common in breast cancer survivors and cannot be managed with standard estrogen replacement therapy (ERT) in these patients. The purpose of this study was to test the efficacy of a comprehensive menopausal assessment (CMA) intervention program in achieving relief of symptoms, the improvement in quality of life (QOL), and sexual functioning in breast cancer survivors. Methods: Using a two-group, randomized controlled design, we assigned 76 postmenopausal breast cancer survivors with at least one severe target symptom either to the intervention group or to a usual-care group. Seventy-two women were evaluable at the end of the study period. The CMA intervention, delivered by a nurse practitioner, focused on symptom assessment, education, counseling and, as appropriate, specific pharmacologic and behavioral interventions for each of the three target symptoms. Psychosocial symptoms were assessed with the use of a self-report screening instrument, and distressed women were referred for counseling if needed. The intervention took place over a 4-month period. Outcomes measured were scores on a composite menopausal symptom scale, the RAND Short Form Health Survey Vitality Scale, and the Cancer Rehabilitation Evaluation System (CARES) Sexual Functioning Scale at baseline and at 4-month follow-up. All statistical tests were two-sided and were performed at the alpha = .05 significance level. Results: Patients receiving the intervention demonstrated statistically significant improvement (P = .0004) in menopausal symptoms but no significant change in vitality (P = .77). Sexual functioning was statistically significantly improved (P = .04) in the treatment group compared with the usual-care group. Conclusions: A clinical assessment and intervention program for menopausal symptom management in breast cancer survivors is feasible and acceptable to patients, leading to reduction in symptoms and improvement in sexual functioning. Measurable improvement in a general QOL measure was not demonstrated.
Treatment of advanced NSCLC: promising results with the FTase inhibitor lonafarnib
Authors: C Carlin
Journal: Thorax (2005)

▴ Kim ES, Kies MS, Fosella FV, et al . Phase II study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in patients with taxane-refractory/resistant non-small cell lung carcinoma. Cancer2005;104:561–9 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Various cell signalling and centromere proteins whose function is perturbed and/or upregulated in human tumours require the addition of a farnesyl pyrophosphate molecule for normal function. Farnesyl transferase (FTase) inhibitors block this step, reduce the function of these oncogenic proteins, and inhibit the growth of a variety of human tumour cell lines. FTase inhibitors are well … [1]: {openurl}?query=rft.jtitle%253DCancer%26rft.stitle%253DCancer%26rft.aulast%253DKim%26rft.auinit1%253DE.%2BS.%26rft.volume%253D104%26rft.issue%253D3%26rft.spage%253D561%26rft.epage%253D569%26rft.atitle%253DPhase%2BII%2Bstudy%2Bof%2Bthe%2Bfarnesyltransferase%2Binhibitor%2Blonafarnib%2Bwith%2Bpaclitaxel%2Bin%2Bpatients%2Bwith%2Btaxane-refractory%252Fresistant%2Bnonsmall%2Bcell%2Blung%2Bcarcinoma.%26rft_id%253Dinfo%253Adoi%252F10.1002%252Fcncr.21188%26rft_id%253Dinfo%253Apmid%252F16028213%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1002/cncr.21188&link_type=DOI [3]: /lookup/external-ref?access_num=16028213&link_type=MED&atom=%2Fthoraxjnl%2F60%2F11%2F894.atom [4]: /lookup/external-ref?access_num=000230631700015&link_type=ISI
Diagnosing Acute Pulmonary Embolism
Authors: IENEKE J. C. HARTMANN, PETRONELLA J. HAGEN, CHRISTIAN F. MELISSANT, PIETER E. POSTMUS, MARTIN H. PRINS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In patients with chronic obstructive pulmonary disease (COPD), differentiating a pulmonary embolism (PE) from an exacerbation of COPD can be difficult, since clinical signs and symptoms of the two conditions overlap. Development of reliable noninvasive or minimally invasive techniques for the diagnosis of PE is, especially in these patients, necessary. In this study we assessed the effect of COPD on the accuracy of the clinical probability estimate (CPE), spiral computed tomographic angiography (SCTA), D-dimer analysis, ventilation perfusion (V˙/Q˙) scintigraphy, and pulmonary angiography for the diagnosis of PE. From May 1997 through March 1998, 627 consecutive patients with suspected PE were investigated in six teaching hospitals. In these patients, D-dimer testing, CPE, V˙/Q˙ scintigraphy, and SCTA and/or pulmonary angiography were performed according to a strict diagnostic protocol. The patients were also independently categorized as having COPD or not. A disagnosis of COPD was established in 91 patients (15%). The prevalence of PE was similar in patients with and without COPD (29% and 31%, respectively), notwithstanding the larger proportion of nondiagnostic V˙/Q˙ scan results in patients with COPD (46% versus 21%, p < 0.001). The distribution of CPEs, diagnostic value of the D-dimer assay and SCTA, and reproducibility of pulmonary angiography were comparable among patients with and without COPD. The presence of COPD does not affect the diagnostic performance of CPE, D-dimer testing, SCTA, or pulmonary angiography. Furthermore, although more nondiagnostic V˙/Q˙ scan results can be expected in the presence of COPD, V˙/Q˙ scintigraphy remains a valuable screening test in patients with COPD.
Virus-induced atherosclerosis.
Authors: C G Fabricant, J Fabricant, M M Litrenta, C R Minick
Journal: The Journal of Experimental Medicine (1978)

Of four groups of chickens, two (groups I and II) were infected with MDV and two were not (groups III and IV). Groups I and III were fed diets low in lipid, and groups II and IV were fed cholesterol-supplemented diets. Striking grossly visible atherosclerotic lesions were seen in large coronary arteries, aortas, and major aortic branches of infected normocholesterolemic and hypercholesterolemic chickens (groups I and II). In contrast, grossly visible atherosclerotic lesions were not seen in uninfected normocholesterolemic chickens (group III), nor in uninfected hypercholesterolemic chickens (group IV). Microscopically, arterial changes in the infected animals were characterized by occlusive fibromuscular intimal thickening which formed fibrous caps overlying areas of atheromatous change. This change closely resembled chronic atherosclerosis in man. These results may have important bearing on our understanding of the etiology and pathogenesis of human arteriosclerosis since there is widespread and persistent infection of human populations with up to five different herpes-viruses.
Toll-like receptor 7 governs interferon and inflammatory responses to rhinovirus and is suppressed by IL-5-induced lung eosinophilia
Authors: Luke Hatchwell, Adam Collison, Jason Girkin, Kristy Parsons, Junyao Li, Jie Zhang, Simon Phipps, Darryl Knight, Nathan W Bartlett, Sebastian L Johnston, Paul S Foster, Peter A B Wark, Joerg Mattes
Journal: Thorax (2015)

<h3>Background</h3> Asthma exacerbations represent a significant disease burden and are commonly caused by rhinovirus (RV), which is sensed by Toll-like receptors (TLR) such as TLR7. Some asthmatics have impaired interferon (IFN) responses to RV, but the underlying mechanisms of this clinically relevant observation are poorly understood. <h3>Objectives</h3> To investigate the importance of intact TLR7 signalling in vivo during RV exacerbation using mouse models of house dust mite (HDM)-induced allergic airways disease exacerbated by a superimposed RV infection. <h3>Methods</h3> Wild-type and TLR7-deficient (<i>Tlr7<sup>−/−</sup></i>) BALB/c mice were intranasally sensitised and challenged with HDM prior to infection with RV1B. In some experiments, mice were administered recombinant IFN or adoptively transferred with plasmacytoid dendritic cells (pDC). <h3>Results</h3> Allergic <i>Tlr7<sup>−/−</sup></i> mice displayed impaired IFN release upon RV1B infection, increased virus replication and exaggerated eosinophilic inflammation and airways hyper reactivity. Treatment with exogenous IFN or adoptive transfer of TLR7-competent pDCs blocked these exaggerated inflammatory responses and boosted IFNγ release in the absence of host TLR7 signalling. TLR7 expression in the lungs was suppressed by allergic inflammation and by interleukin (IL)-5-induced eosinophilia in the absence of allergy. Subjects with moderate-to-severe asthma and eosinophilic but not neutrophilic airways inflammation, despite inhaled steroids, showed reduced TLR7 and IFNλ2/3 expression in endobronchial biopsies. Furthermore, TLR7 expression inversely correlated with percentage of sputum eosinophils. <h3>Conclusions</h3> This implicates IL-5-induced airways eosinophilia as a negative regulator of TLR7 expression and antiviral responses, which provides a molecular mechanism underpinning the effect of eosinophil-targeting treatments for the prevention of asthma exacerbations.