tbuckley/cabot-search huggingface dataset:
Nonenzymatic addition of glucocorticoids to lens proteins in steroid-induced cataracts.
Authors: S Manabe, R Bucala, A Cerami
Journal: Journal of Clinical Investigation (1984)

A frequent manifestation of long-term glucocorticoid administration is the occurrence of posterior subcapsular cataracts. The molecular basis for this effect has not yet been elucidated. The addition of prednisolone to the rat lens in culture results in a time- and concentration-dependent lens opacification that correlates with the formation of covalent prednisolone-lens protein adducts. Prednisolone adduct formation was analyzed by [3H]prednisolone incorporation and by immunoprecipitation with antiserum specific for proteins modified by the nonenzymatic addition of prednisolone. In the rat lens, these adducts were localized in both the water-soluble and urea-soluble lens protein fractions. Gel electrophoresis and fluorography revealed that the most extensively modified proteins were two crystallins subunits. Lens proteins from 33 normal and cataractous human lenses were fractionated and analyzed for the presence of prednisolone-protein adducts by competitive radioimmunoassay. Adducts were detected only in those samples derived from glucocorticoid-induced cataractous lenses. We conclude that elevated glucocorticoid levels lead to the formation of glucocorticoid-lens protein adducts both in vitro and in vivo. Lens protein modification by glucocorticoids may lead to sufficient biochemical or structural alterations so as to result in cataract formation. The ability of glucocorticoids to form adducts with proteins in vivo also may play a role in some of the other toxic manifestations of long-term glucocorticoid therapy.
Lipolysis and lipogenesis from glucose in human fat cells of different sizes
Authors: R. B. Goldrick, G. M. McLoughlin
Journal: Journal of Clinical Investigation (1970)

Lipogenesis from glucose and lipolysis in human omental and subcutaneous fat cells were studied as functions of adipose cell size and number in adult females. Since subcutaneous fat cells were larger than those prepared from the greater omentum, a comparison could be made of the metabolism of different sizes of cells within individual subjects. Rates per cell of glyceride-glycerol and glyceride-fatty acid synthesis from glucose were similar in omental and subcutaneous fat cells incubated in the presence or absence of insulin. However, subcutaneous fat cells exhibited higher rates of basal lipolysis than omental fat cells and these differences were maintained when lipolysis was stimulated with theophylline. Different rates of lipolysis were not demonstrable after incubations with epinephrine, indicating that subcutaneous fat cells were less responsive to this hormone than smaller omental fat cells. Correlation and partial correlation analysis showed that differences in basal and theophylline-stimulated lipolysis between fat cells prepared from different subjects and between omental and subcutaneous fat cells could be accounted for by differences in adipose cell volume. In subcutaneous fat cells highly significant intercorrelations were demonstrated between cell volume, basal lipolysis, and the basal conversion of glucose to glyceride-glycerol. There was no correlation between fat cell volume, age, or relative obesity and the effects of theophylline or insulin on lipolysis or lipogenesis from glucose in vitro when the data were expressed as percentage changes above basal values.
Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid
Authors: Stefan Worgall, Anja Krause, Michael Rivara, Kyung-Kim Hee, Enrico V. Vintayen, Neil R. Hackett, Peter W. Roelvink, Joseph T. Bruder, Thomas J. Wickham, Imre Kovesdi, Ronald G. Crystal
Journal: Journal of Clinical Investigation (2005)

Pseudomonas aeruginosa is an important opportunistic pathogen that can cause chronic and often life-threatening infections of the respiratory tract, particularly in individuals with cystic fibrosis (CF). Because infections with P. aeruginosa remain the major cause of the high morbidity and mortality of CF, a vaccine against P. aeruginosa would be very useful for preventing this disorder. The outer membrane protein F (OprF) of P. aeruginosa is a promising vaccine candidate and various B cell epitopes within OprF have been identified. Given that adenovirus (Ad) vectors have strong immunogenic potential and can function as adjuvants for genetic vaccines, the present study evaluates the immunogenic and protective properties of a novel replication-deficient Ad vector in which the Ad hexon protein was modified to include a 14–amino acid epitope of P. aeruginosa OprF (Epi8) in loop 1 of the hypervariable region 5 of the hexon (AdZ.Epi8). Immunization of C57BL/6 mice with AdZ.Epi8 resulted in detectable serum anti–P. aeruginosa and anti-OprF humoral responses. These responses were haplotype dependent, with higher serum anti-OprF titers in CBA mice than in BALB/c or C57BL/6 mice. AdZ.Epi8 induced Epi8-specific IFN-γ–positive CD4 and CD8 T cell responses and resulted in protection against a lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeated administration of AdZ.Epi8 resulted in boosting of the anti-OprF humoral and anti-Epi8 cellular response, whereas no boosting effect was present in the response against the transgene β-galactosidase. These observations suggest that Ad vectors expressing pathogen epitopes in their capsid will protect against an extracellular pathogen and will allow boosting of the epitope-specific humoral response with repeated administration, a strategy that should prove useful in developing Ad vectors as vaccines where humoral immunity will be protective.
Comprehensive MicroRNA Profiling for Head and Neck Squamous Cell Carcinomas
Authors: Angela B.Y. Hui, Michelle Lenarduzzi, Tiffaney Krushel, Levi Waldron, Melania Pintilie, Wei Shi, Bayardo Perez-Ordonez, Igor Jurisica, Brian O'Sullivan, John Waldron, Pat Gullane, Bernard Cummings, Fei-Fei Liu
Journal: Clinical Cancer Research (2010)

The objective of this study is to investigate the significance of microRNAs (miRNA) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).A global miRNA profiling was done on 51 formalin-fixed archival HNSCC samples using quantitative reverse transcription-PCR approach, correlated with patients' clinical parameters. Functional characterization of HNSCC-associated miRNAs was conducted on three HNSCC cell lines. Cell viability and proliferation were investigated using MTS and clonogenic assays, respectively; cell cycle analyses were assessed using flow cytometry.Thirty-eight of the 117 (33%) consistently detected miRNAs were significantly differentially expressed between malignant versus normal tissues. Concordant with previous reports, overexpression of miR-21, miR-155, let-7i, and miR-142-3p and underexpression of miR-125b and miR-375 were detected. Upregulation of miR-423, miR-106b, miR-20a, and miR-16 as well as downregulation of miR-10a were newly observed. Exogenous overexpression of miR-375 in HNSCC cell lines reduced proliferation and clonogenicity and increased cells in sub-G(1). Similar cellular effects were observed in knockdown studies of the miR-106b-25 cluster but with accumulation of cells in G(1) arrest. No major difference was detected in miRNA profiles among laryngeal, oropharyngeal, or hypopharyngeal cancers. miR-451 was found to be the only significantly overexpressed miRNA by 4.7-fold between nonrelapsed and relapsed patients.We have identified a group of aberrantly expressed miRNAs in HNSCC and showed that underexpression of miR-375 and overexpression of miR-106b-25 cluster might play oncogenic roles in this disease. Further detailed examinations of miRNAs will provide opportunities to dissect the complex molecular abnormalities driving HNSCC progression.
Angiogenic effect of intramuscular administration of basic fibroblast growth factor in atrophied muscles: an experimental study in the rat * Commentary
Authors: A Efthimiadou, N K Nikolettos, M Lambropoulou, N Papadopoulos, E Kontoleon
Journal: British Journal of Sports Medicine (2006)

Background: Although angiogenic therapy using recombinant growth factors holds much hope for the treatment of ischaemic diseases, there are still many unanswered questions, including its effectiveness on atrophic muscles. Objective: To evaluate the angiogenic effects of intramuscularly administered basic fibroblast growth factor (b-FGF) on normal gastrocnemius muscles of rats and atrophic gastrocnemius muscles after tenotomy. Methods: Forty rats were divided into groups as follows: group A, controls; group B, injected with 1 μg b-FGF; group C, tenotomy performed on the right gastrocnemius muscle; group D, tenotomy and 1 μg b-FGF. Mouse anti-rat CD31 antibody was used to evaluate the number of blood vessels present in histological preparations. Results: There was a significant (p&lt;0.01) decrease in the number of blood vessels compared with the controls in the atrophic muscles of group C. This was similar to the decrease in muscle weight in this group. However, there was a significant (p&lt;0.01) increase in the number of blood vessels compared with the controls in groups B and D. Similarly, there was a significant (p&lt;0.01) increase in the number of blood vessels in group D compared with the atrophic muscles in group C. Conclusion: Intramuscular administration of b-FGF increases angiogenesis in both normal and atrophic rat gastrocnemius muscles at the injection area.
A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis
Authors: Yuan-Jen Wang, Shou-Dong Lee, Mao-Chih Hsieh, Han-Chieh Lin, Fa-Yauh Lee, Shyh-Haw Tsay, Yang-Te Tsai, Oliver Yoa-Pu Hu, Ming-Lu King, Kwang-Juei Lo
Journal: Journal of Hepatology (1994)
Morbidity and Mortality Associated With the July 1980 Heat Wave in St Louis and Kansas City, Mo
Authors: T. Stephen Jones
Journal: JAMA (1982)

The morbidity and mortality associated with the 1980 heat wave in St Louis and Kansas City, Mo, were assessed retrospectively. Heat-related illness and deaths were identified by review of death certificates and hospital, emergency room, and medical examiners' records in the two cities. Data from the July 1980 heat wave were compared with data from July 1978 and 1979, when there were no heat waves. Deaths from all causes in July 1980 increased by 57% and 64% in St Louis and Kansas City, respectively, but only 10% in the predominantly rural areas of Missouri. About one of every 1,000 residents of the two cities was hospitalized for or died of heat-related illness. Incidence rates (per 100,000) of heatstroke, defined as severe heat illness with documented hyperthermia, were 26.5 and 17.6 for St Louis and Kansas City, respectively. No heatstroke cases occurred in July 1979. Heatstroke rates were ten to 12 times higher for persons aged 65 years or older than for those younger than 65 years. The ratios of age-adjusted heatstroke rates were approximately 3:1 for nonwhite v white persons and about 6:1 for low v high socioeconomic status. Public health preventive measures in future heat waves should be directed toward the urban poor, the elderly, and persons of other-than-white races.
High Prevalence of Cardiac Parvovirus B19 Infection in Patients With Isolated Left Ventricular Diastolic Dysfunction
Authors: C. Tschöpe, C.-T. Bock, M. Kasner, M. Noutsias, D. Westermann, P.-L. Schwimmbeck, M. Pauschinger, W.-C. Poller, U. Kühl, R. Kandolf, H.-P. Schultheiss
Journal: Circulation (2005)

Background— The etiology of left ventricular (LV) isolated diastolic dysfunction often remains unclear. In the present study, we report a strong association between parvovirus B19 (PVB19) genomes and isolated LV diastolic dysfunction. Methods and Results— In 70 patients (mean±SD age, 43±11 years) admitted with exertional dyspnea and/or reduced exercise tolerance despite preserved LV systolic contractility (ejection fraction=68%), isolated diastolic dysfunction was clinically suspected. Patients with classic risk factors for diastolic dysfunction such as hypertension, coronary heart disease, diabetes mellitus, or pulmonary disease had been excluded. Diastolic function was assessed by echocardiography and LV and RV catheterization. Endomyocardial biopsies (EMBs) were analyzed for the presence of storage or infiltrative diseases or myocarditis, including molecular screening for cardiotropic virus genomes. In a substudy of 24 patients who reported atypical angina, coronary endothelial function was additionally investigated with a coronary Doppler flow-wire technique. In 37 of 70 patients (53%), isolated diastolic dysfunction was confirmed as the cause of their clinical symptoms. No evidence for cardiac storage or infiltrative diseases was found in these cases, but in 35 of 37 of these patients (95%), cardiotropic virus genomes were detected in EMBs ( P &lt;0.001). PVB19 was the most frequent pathogen in 31 of 37 patients (84%). In a subgroup of 10 patients with diastolic dysfunction and coexisting endothelial dysfunction, all 10 (100%) were PVB19 positive. Conclusions— PVB19 genomes were predominant in patients with unexplained, isolated diastolic dysfunction. A strong association with the incidence of endothelial dysfunction was obvious, consistent with the hypothesis that PVB19-induced endothelial dysfunction may be a possible pathomechanism underlying diastolic dysfunction.
Protective and determining factors for the overall lipid peroxidation in ultraviolet A1-irradiated fibroblasts: in vitro and in vivo investigations
Authors: J. Dissemond, L.A. Schneider, P. Brenneisen, K. Briviba, J. Wenk, M. Wlaschek, K. Scharffetter-Kochanek
Journal: British Journal of Dermatology (2003)

Lipid peroxidation (LPO) is one major effector mechanism by which ultraviolet (UV) A contributes to photoageing and the promotion of skin cancer. It is a fingerprint of photo-oxidative stress within the skin, and is initiated by several pathways, with different reactive oxygen species (ROS) and iron ions being involved.To elucidate factors involved in UVA1-induced LPO in human dermal fibroblasts and mouse dermis, and the role of antioxidant enzymes in protecting cells against LPO.Using a highly sensitive high-performance liquid chromatography procedure, we measured malondialdehyde (MDA), a specific metabolic tracer molecule for LPO, to determine the overall LPO produced by a given UVA1 dose in vitro and in vivo. By using the iron chelator desferrioxamine (DFO), the hydroxyl radical scavenger dimethylsulphoxide (DMSO) and fibroblasts that specifically overexpress single antioxidant enzymes, we further indirectly assessed the protective effect of manganese superoxide dismutase (MnSOD), catalase and phospholipid hydroperoxide glutathione peroxidase (PHGPx) as well as the relative importance of different ROS and the role of transitional iron for the total amount of LPO induced by a distinct UVA dose.UVA1 irradiation resulted in a time- and dose-dependent increase in MDA levels in vitro, and the in vitro results were shown to have in vivo relevance. Fibroblasts incubated with DFO or DMSO produced lower levels of MDA than controls, as did fibroblasts overexpressing MnSOD, catalase or PHGPx.The cellular iron pool and hydroxyl radicals were the most important determining factors for the total amount of MDA produced after a given UVA1 dose, and PHGPx overexpression had the greatest protective effect against LPO.
Reciprocal altered expression of T-cadherin and P-cadherin in psoriasis vulgaris
Authors: S. Zhou, N. Matsuyoshi, T. Takeuchi, Y. Ohtsuki, Y. Miyachi
Journal: British Journal of Dermatology (2003)

The most characteristic change in psoriasis vulgaris is markedly increased, persistent keratinocyte proliferation. The underlying mechanism of excessive epidermal growth is controversial. We previously found and reported that T-cadherin was expressed in keratinocytes and confined to the basal layer of mouse and human skin. Invasive cutaneous squamous cell carcinoma showed a loss of T-cadherin expression. Another study showed that T-cadherin was a negative growth regulator of epidermal growth factor in T-cadherin transfectant neuroblastoma cells.To obtain insight into the role of T-cadherin in keratinocyte proliferation and to investigate further the pathogenesis of psoriasis vulgaris, we examined the expression of T-cadherin, as well as E- and P-cadherin, in psoriasis vulgaris.Four untreated active psoriatic skin samples from psoriasis vulgaris patients and four normal human skin samples from plastic surgery were collected, cryosectioned and immunohistochemically stained by antihuman T-, P- and E-cadherin antibodies. Further, the immunofluorescence intensities of T- and P-cadherin on the basal layer of the epidermis were quantitatively measured by the histogram function of LSM 510 software installed in a Zeiss laser scanning confocal microscope. The data were statistically analysed by Student's t-test.It was observed that T-cadherin was weakly and discontinuously expressed on the basal layer of psoriatic skin, while it was intensively expressed on all basal keratinocytes in normal human skin. In contrast, P-cadherin was strongly expressed throughout the entire epidermal layer in psoriatic skin samples, although its expression is restricted to the basal cell layer in normal human skin. There were no obvious differences in E-cadherin expression between normal human skin and psoriatic skin. Statistical analyses showed that the immunofluorescence intensity of T-cadherin in the basal cell layer of psoriatic skin (35 +/- 9.08) was significantly decreased compared with that in normal human skin (131.75 +/- 3.49, P = 2.46 x 10(-6)). There was a significant increase (P = 0.00139) in the immunofluorescence intensity of P-cadherin in the basal layer of psoriatic skin (68.25 +/- 12.13) compared with normal human skin (26 +/- 4.90).The present study demonstrates that there is downregulation of T-cadherin expression and upregulation of P-cadherin expression in psoriatic skin, which are considered to be involved in the hyperproliferation of keratinocytes in psoriasis vulgaris.
Guidelines for prescribing azathioprine in dermatology
Authors: A.V. ANSTEY, S. WAKELIN, N.J. REYNOLDS
Journal: British Journal of Dermatology (2004)

Azathioprine has been available as an immunosuppressive agent for over 40 years, and current routine usage in dermatology is not restricted to licensed indications. Advances in understanding the metabolic fate of azathioprine have led to significant changes in prescribing practice and toxicity monitoring by U.K. dermatologists. The current state of knowledge concerning the use of azathioprine in dermatology is summarized, with identification of strength of evidence. Clinical indications and contraindications for azathioprine usage in dermatology are identified. Evidence‐based recommendations are made for routine safety monitoring of patients treated with azathioprine, including pretreatment assessment of red blood cell thiopurine methyltransferase activity.
Size of sentinel-node metastasis and chances of non-sentinel-node involvement and survival in early stage vulvar cancer: results from GROINSS-V, a multicentre observational study
Authors: Maaike H Oonk, Bettien M van Hemel, Harry Hollema, Joanne A de Hullu, Anca C Ansink, Ignace Vergote, René H Verheijen, Angelo Maggioni, Katja N Gaarenstroom, Peter J Baldwin, Eleonora B van Dorst, Jacobus van der Velden, Ralph H Hermans, Hans W van der Putten, Pierre Drouin, Ingo B Runnebaum, Wim J Sluiter, Ate G van der Zee
Journal: The Lancet Oncology (2010)
Tests for Two Trees Using Likelihood Methods
Authors: Edward Susko
Journal: Molecular Biology and Evolution (2014)

This article considers two similar likelihood-based test statistics for comparing two fixed trees, the Kishino-Hasegawa (KH) test statistic and the likelihood ratio (LR) statistic, as well as a number of different methods for determining thresholds to declare a significant result. An explanation is given for why the KH test, which uses the KH test statistic and normal theory thresholds, need not give correct type I error probabilities under the appropriate null hypothesis. Simulations show that the KH test tends to give much smaller type I error probabilities than expected. The article presents a computationally efficient normal-theory parametric bootstrap method for determining better KH test statistic thresholds. For the LR statistic, existing mixture of chi-squares results for determining thresholds are extended to cases in which a tree with two or three zero edge-lengths exhibits the two trees being compared. The resulting chi-bar test and use of the KH test statistic with normal bootstrap are shown through simulation to give good performance but are more difficult to implement than the KH test. Two conservative approaches are presented which require only log likelihoods and simple chi-square thresholds. While they did not perform as well as chi-bar and normal bootstrap methods in the simulations considered, they gave better performance than the KH test and have just as simple an implementation. As a by-product of parametric bootstrap considerations, an adjustment to the Swofford-Olsen-Waddell-Hillis (SOWH) test is proposed.
Type 2 inositol 1,4,5-trisphosphate receptor modulates bile salt export pump activity in rat hepatocytes
Authors: Emma A. Kruglov, Samir Gautam, Mateus T. Guerra, Michael H. Nathanson
Journal: Hepatology (2011)

Bile salt secretion is mediated primarily by the bile salt export pump (Bsep), a transporter on the canalicular membrane of the hepatocyte. However, little is known about the short-term regulation of Bsep activity. Ca(2+) regulates targeting and insertion of transporters in many cell systems, and Ca(2+) release near the canalicular membrane is mediated by the type II inositol 1,4,5-trisphosphate receptor (InsP3R2), so we investigated the possible role of InsP3R2 in modulating Bsep activity. The kinetics of Bsep activity were monitored by following secretion of the fluorescent Bsep substrate cholylglycylamido-fluorescein (CGamF) in rat hepatocytes in collagen sandwich culture, an isolated cell system in which structural and functional polarity is preserved. CGamF secretion was nearly eliminated in cells treated with Bsep small interfering RNA (siRNA), demonstrating specificity of this substrate for Bsep. Secretion was also reduced after chelating intracellular calcium, inducing redistribution of InsP3R2 by depleting the cell membrane of cholesterol, or reducing InsP3R function by either knocking down InsP3R2 expression using siRNA or pharmacologic inhibition using xestospongin C. Confocal immunofluorescence showed that InsP3R2 and Bsep are in close proximity in the canalicular region, both in rat liver and in hepatocytes in sandwich culture. However, after knocking down InsP3R2 or inducing its dysfunction with cholesterol depletion, Bsep redistributed intracellularly. Finally, InsP3R2 was lost from the pericanalicular region in animal models of estrogen- and endotoxin-induced cholestasis.These data provide evidence that pericanalicular calcium signaling mediated by InsP3R2 plays an important role in maintaining bile salt secretion through posttranslational regulation of Bsep, and suggest that loss or redistribution of InsP3R2 may contribute to the pathophysiology of intrahepatic cholestasis.
Generation of tumor-infiltrating lymphocytes from pancreatic cancer lesions for cellular therapy
Authors: Qingda Meng, Elena B Rangelova, Liu zhenjiang, Thomas Poiret, Bartek Jiri, Caroline Verbeke, Ernest Dodoo, Ralf Segersvärd, Markus Maeurer
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts The generation of T lymphocytes with specific reactivity against autologous tumor is a prerequisite for effective adoptive transfer therapies. Pancreatic cancer-specific lymphocyte cultures from tumor infiltrating lymphocytes (TILs) may represent a viable source of T cells for the