tbuckley/cabot-search huggingface dataset:
miRNA-mediated Silencing in Hepatocytes Can Increase Adaptive Immune Responses to Adenovirus Vector-delivered Transgenic Antigens
Authors: Matthias W Kron, Sigrid Espenlaub, Tatjana Engler, Reinhold Schirmbeck, Stefan Kochanek, Florian Kreppel
Journal: Molecular Therapy (2011)

Adenovirus vectors based on human serotype 5 can induce potent CD8 T cell responses to vector-encoded transgenic antigens. However, the individual contribution of different cell types expressing antigen upon adenovirus vector injection to the generation of antigen-directed adaptive immune responses is poorly understood so far. We investigated the role of hepatocytes, skeletal muscle, and hematopoietic cells for the induction of cellular and humoral immune responses by miRNA-mediated tissue-specific silencing of antigen expression. Using hepatitis B small surface antigen (HBsAg) as the vector-encoded transgene we show that adenovirus vector dissemination from an intramuscular (i.m.) injection site into the liver followed by HBsAg expression in hepatocytes can limit early priming of CD8 T cells and the generation of anti-HBsAg antibody responses. However, hepatocyte-specific miRNA122a-mediated silencing of HBsAg expression overcame these limitations. Early clonal expansion of K(b)/S(190-197)-specific CD8 T cells was significantly enhanced and improved polyfunctionality of CD8 T cells was found. Furthermore, miRNA122a-mediated antigen silencing induced significantly higher anti-HBsAg antibody titers allowing an up to 100-fold vector dose reduction. These results indicate that miRNA-mediated regulation of antigen expression in the context of adenovirus vectors can significantly improve transgene product-directed immune responses. This finding could be of interest for future adenovirus vaccine vector development.
S117 4 h cough frequency monitoring with the Leicester Cough Monitor
Authors: K. K. Lee, A. Savani, S. Matos, C. Woods, I. D. Pavord, S. S. Birring
Journal: Thorax (2010)

<h3>Introduction</h3> The Leicester Cough Monitor (LCM) is a validated 24-h automated cough frequency monitor. Shorter recordings are more convenient for patients and take less time to analyse but their validity for assessing cough is not known. We assessed the relationship between short duration and 24-h recordings. <h3>Methods</h3> 100 patients (57 females) with chronic cough underwent 24-h ambulatory cough frequency monitoring with the LCM. Patients completed diaries to identify awake and sleep periods. Cough frequency was determined by automated analysis and presented as 24-h cough frequency (CF<sub>24</sub>), awake cough frequency, sleep cough frequency, and short duration (1–6 h). Subjective cough severity was assessed by cough visual analogue scale and quality of life questionnaire (Leicester Cough Questionnaire, LCQ). The optimal short cough recording duration was determined by assessing its relationship with awake cough frequency and subjective cough severity. The responsiveness of short duration recordings was tested in 20 patients undergoing trials of therapy. <h3>Results</h3> The median (IQR) 24-h cough frequency was 11.5 (5.8 to 26.6) coughs/h, awake cough frequency 13.2 (7.6 to 37.5) coughs/h and sleep cough frequency 4.2 (1.0 to 9.2) coughs/h. 4-h cough counts correlated strongly with both awake and 24-h cough counts; r<sup>2</sup>=0.88 and r<sup>2</sup>=0.87 respectively (Abstract S117 Figure 1). There was a moderate relationship between 4-h cough frequency (CF<sub>4</sub>) and LCQ and cough VAS (r=−0.48, p&lt;0.001 and 0.49, p&lt;0.001) which was comparable to that between awake cough frequency and LCQ and cough VAS. The effect size of change in CF<sub>4</sub> after therapeutic trials was 0.55. <h3>Conclusions</h3> Shorter duration cough frequency recordings with the LCM accurately reflect daytime and 24-h cough frequency in patients with chronic cough. They can be used to assess daytime cough frequency and the response to trials of therapy.
Wool follicle matrix cells: culture conditions and keratin expression<i>in vitro</i>
Authors: E.J. BATES, N.M. PENNO, P.I. HYND
Journal: British Journal of Dermatology (1999)

Wool follicle matrix cell cultures were initiated as explants from Tukidale (carpet wool) sheep primary follicle bulbs after removal of the outer root sheath. Successful explantation required coculture on collagen with intact dermal papillae. Cells had a typical epidermal morphology (pavements of flattened. polyhedral cells). Extracellular matrix from dermal papillae, conditioned media, separation of dermal papilla from bulb matrices by tissue culture inserts and feeder layers were unable to support matrix cell explantation. Cultures could be maintained for up to 14 passages during which time the cells became larger with an increased cytoplasmic/nuclear ratio and irregular outline. Proliferation of matrix cells was greater on laminin than with either collagen type I or type IV. Proliferation was considerably reduced under serum-free conditions. This was most apparent at low calcium (0.09 mmol/L). By Northern hybridization matrix cells were found to express keratin K18 at all stages of culture. Keratin K 1.15 expression was evident by the tenth passage. The wool-specific keratin K2.10 was not detected. The data demonstrate that successful wool matrix cell culture is achievable. Keratin gene expression occurs in these cells and varies with the stage of culture.
Methotrexate and its effect on the anti-GAD titre in two patients with rheumatoid arthritis and diabetes mellitus
Authors: A W van Deutekom, M T Nurmohamed, M J L Peters, I C van Eijk, B A C Dijkmans, D Hamann, R J Heine, S Simsek
Journal: Annals of the Rheumatic Diseases (2008)

Methotrexate (MTX) is the anchor drug in treatment of patients with rheumatoid arthritis (RA)1 2 and may reduce levels of rheumatoid factor (RF).3 4 Moreover, treatment of patients with RA with biological agents—that is, tumour necrosis factor α (TNFα) antagonist, is presently combined with MTX to reduce the formation of antibodies against the biological agents.

We describe two patients with known latent autoimmune diabetes of the adult and concomitant RA who showed a marked decline in anti-glutamic acid decarboxylase (GAD) titres after receiving MTX treatment.

The first case is a 68-year-old woman who has had anti-GAD positive diabetes since the age of 47, which was poorly controlled, without hypertension and a body mass …
An RNA-seq-based Gene Expression Profiling of Radiation-induced Tumorigenic Mammary Epithelial Cells
Authors: Lina Ma, Linghu Nie, Jing Liu, Bing Zhang, Shuhui Song, Min Sun, Jin Yang, Yadong Yang, Xiangdong Fang, Songnian Hu, Yongliang Zhao, Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2012)

Abstract Immortality and tumorigenicity are two distinct characteristics of cancers. Immortalization has been suggested to precede tumorigenesis. To understand the molecular mechanisms of tumorigenicity and cancer progression in mammary epithelium, we established a tumorigenic cell model by means of heavy-ion radiation of an immortal cell model, which was created by overexpressing the human telomerase reverse transcriptase (hTERT) in normal human mammary epithelial cells. We examined the expression profile of this tumorigenic cell line (T_hMEC) using the hTERT-overexpressing immortal cell line (I_hMEC) as a control. In-depth RNA-seq data was generated by using the next-generation sequencing (NGS) platform (Life Technologies SOLiD3). We found that house-keeping (HK) and tissue-specific (TS) genes were differentially regulated during the tumorigenic process. HK genes tended to be activated while TS genes tended to be repressed. In addition, the HK genes and TS genes tended to contribute differentially to the variation of gene expression at different RPKM (gene expression in reads per exon kilobase per million mapped sequence reads) levels. Based on transcriptome analysis of the two cell lines, we defined 7053 differentially-expressed genes (DEGs) between immortality and tumorigenicity. Differential expression of 20 manually-selected genes was further validated using qRT-PCR. Our observations may help to further our understanding of cellular mechanism(s) in the transition from immortalization to tumorigenesis.
The New Genetics
Authors: Robert A. Goyer
Journal: JAMA (1967)

<h3>Evolution and Human Behavior,</h3> by Alexander Alland, Jr., 243 pp, 37 illus, paper $1.45, cloth $5.95. Garden City, NY: Natural History Press, 1967. Expansion of knowledge in molecular or biochemical genetics in recent years has been virtually explosive. Unless one is working in an area immediately related to the new science, it is difficult to maintain a broad and up-to-date perspective of new developments. Two recent books,<i>New Genetics</i>by Leonard Engel and<i>Evolution and Human Behavior</i>by Alexander Alland, are brief, easily read reviews of present-day genetics. Both are written for the lay or professional person who desires a succinct and not too difficult elucidation of the modern science of heredity. They differ, however, in their orientation. Leonard Engel's monograph focuses on the very essence of life, the nature of the gene and chemistry of deoxyribonucleic and ribonucleic acids and transmission of genetic information at the cellular level. After
Continuous arteriovenous haemofiltration in patients with hepatic encephalopathy and renal failure.
Authors: A Davenport, E J Will, M S Losowsky, S Swindells
Journal: BMJ (1987)

Une observation d'encephalopathie hepatique et d'insuffisance renale apres intoxication volontaire (100 comprimes de paracetamol). Traitement par hemofiltration selon 2 methodes differentes. Pendant l'hemofiltration par machine Gambro FH77, la pression intracrânienne est augmentee pendant la premiere heure, puis diminuee. Lors de l'hemofiltration arterioveineuse continue la pression intracrânienne est inchangee. Apres 5 j de ces traitements alternes la diurese se retablit et la malade se retablit rapidement sans sequelles
Utilization of adipose tissue biopsy in characterizing human halogenated hydrocarbon exposure.
Authors: H A Anderson
Journal: Environmental Health Perspectives (1985)

Halogenated hydrocarbons have been successfully utilized for pest control in agriculture and public health. In industry, the polychlorinated biphenyls (PCBs) have been particularly useful. Unfortunately, residues have proven persistent and have been found widely dispersed in the environment. Because they have chemical properties that favor bioaccumulation, it is not surprising that many have been identified in animals and man. Such findings prompted public health concern and initiated review of potential adverse health impacts. In many instances this process has led to total prohibition of use or strict limitations. Highly lipophilic, the primary accumulation site in humans is adipose tissue. Analysis of adipose samples remains the preferred biologic index for estimating exposure. Improved instrumentation has lowered the limit of detection and improved the accuracy of quantification. Accumulated population experience has helped develop understanding of the dynamics of tissue partitioning in humans. Once such relationships have been adequately described, other less invasive procedures may be more confidently used for general surveillance purposes. Whenever adipose tissue is obtained, the blood compartment should also be sampled and the relationship reported. We have only begun to investigate the resulting partition ratio as an investigative tool.
An Extended 10-Core Transrectal Ultrasonography Guided Prostate Biopsy Protocol Improves the Detection of Prostate Cancer
Authors: Saadettin Yilmaz Eskicorapci, Dilek Ertoy Baydar, Cem Akbal, Mustafa Sofikerim, Mert Günay, Sinan Ekici, Haluk Ozen
Journal: European Urology (2003)
Scavenging of Reactive Oxidative Species (ROS) Generated by Pollen NADPH Oxidases Inhibits Th2 and Th17 Cytokine Production from Johnson Grass (JG) Sensitized Human Peripheral Blood Mononuclear Cells (PBMCs)
Authors: M.C. Saavedra, N.G. Dharajiya, D.R. Redding, I. Boldogh, C.Y. Lee, S. Sur
Journal: Journal of Allergy and Clinical Immunology (2007)
Norwalk Gastroenteritis: A Community Outbreak Associated with Bakery Product Consumption
Authors: Joel N. Kuritsky, Michael T. Osterholm, Harry B. Greenberg, Jack A. Korlath, Janice R. Godes, Craig W. Hedberg, Jan C. Forfang, Albert Z. Kapikian, John C. McCULLOUGH, Karen E. White
Journal: Annals of Internal Medicine (1984)

From 23 to 26 August 1982, a gastrointestinal illness occurred among 129 of 248 (52%) persons interviewed who had attended four social events in the Minneapolis-St. Paul area. The median incubation period was 36 hours, and symptoms included diarrhea, nausea, headache, and vomiting. Findings of a food-specific questionnaire given to attendants of the four events confirmed that consumption of cake and frosting was significantly associated with development of the illness (odds ratio, 7.9 to 48.3; p = 0.006 to 0.00001). All cake items were purchased from a single bakery, where the employee who had prepared the frosting had had onset of diarrhea and vomiting on August 20. Given an approximate 60% attack rate among persons who ate frosted items, we estimate that 3000 outbreak-associated cases occurred. Serologic analysis confirmed that 17 of 25 ill persons had fourfold or greater rises in their antibody titer to Norwalk virus. Thus, foodborne transmission of Norwalk virus can result from contamination by a single foodhandler.
Effect of Proximal Vagotomy and Roux-en-Y Diversion on Gastric Emptying Kinetics in Asymptomatic Patients
Authors: J. L. URBAIN, F. PENNINCKX, J. A. SIEGEL, P. VANDENBORRE, E. VAN CUTSEM, V. VANDENMAEGDENBERGH, M. DE ROO
Journal: Clinical Nuclear Medicine (1990)

The role of the distal stomach in gastric emptying was studied. Ten patients with proximal gastric vagotomy (PV) and 10 age-matched patients with Roux-en-Y gastro-jejunostomy (R-Y) were compared with 10 healthy controls. Gastric emptying of solids and liquids was determined by the use of Tc-99m SC scrambled eggs and In-111 DTPA. In PV, gastric emptying of both solids and liquids was delayed; the prolongation with solids was mainly accounted for by an abnormal lag phase. In R-Y patients, no lag phase was observed, and the solid emptying curve pattern was characterized by early rapid emptying followed by very slow emptying. Both the solid and liquid phases were prolonged. The lag phase is affected by proximal vagotomy and is mainly determined by the distal stomach, which appears to be essential for normal emptying.
High incidence of false‐positive <i>Aspergillus</i> galactomannan test in multiple myeloma
Authors: Yasuo Mori, Yoji Nagasaki, Kenjiro Kamezaki, Katsuto Takenaka, Hiromi Iwasaki, Naoki Harada, Toshihiro Miyamoto, Yasunobu Abe, Nobuyuki Shimono, Koichi Akashi, Takanori Teshima
Journal: American Journal of Hematology (2010)

Invasive aspergillosis (IA) remains one of the most significant causes of morbidity and mortality in patients with hematological malignancies undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT), mainly due to the difficulty in its early diagnosis. Monitoring of galactomannan (GM) antigen, an exoantigen of Aspergillus, in the blood by sandwich ELISA is a useful and noninvasive method for early diagnosis of IA. The GM test has a sensitivity of 67-100% with a specificity of 81-99% in neutropenic patients and allogeneic transplant recipients [1-3]. Although it has been widely used as a diagnostic criterion for IA [4,5], one of the major limitations of this assay is false-positivity, particularly in pediatric patients [1], patients with graft-versus-host disease (GVHD) [6,7], and those taking dietary GM [8,9] or fungus-derived antibiotics, such as piperacillin-tazobactam (PIPC/TAZ) [10-12].
A SIMPLE TECHNIQUE FOR PHOTOGRAPHY OF PATHOLOGICAL SPECIMENS
Authors: C. J. C. Earl
Journal: BMJ (1932)

entiate the rheumatic and syphilitic cases.It is very rarely that this distinction cannot be made with certainty, though sometimes it may be more difficult to differentiate the atheromatous and syphilitic cases.One reason for this contrast is the association of syphilitic aortic incompetence with angina pectoris.In both groups of non- rheumatic patients this was a common finding; fre- quently, indeed, it was a main presenting symptom, and occurred in 40 per cent.In those with syphilis, nocturnal angina was not uncommon, and often the pain lasted for loniger than the usual anginia of effort.On the other hand, angina occurred in less than 5 per cent. of the rheumatic patients.These were mostly men with an average age of 45, and all but one had aortic stenosis. SUMMARYIn a series of cases with disease of the aortic valves, the condition was due to rheumatism in 200, to syphilis in 55, to atheroma in 20, and to all other causes in 21 cases.
Cardiovascular complications during exercise training of cardiac patients.
Authors: W L Haskell
Journal: Circulation (1978)

The occurrence of major cardiovascular complications during exercise training of cardiac patients in 30 cardiac rehabilitation programs in North America was determined by questionnaire. These programs conducted medically supervised cardiac exercise classes in 103 locations and reported information on 13,570 participants who accumulated a total of 1,629,634 patient hours of supervised exercise. Cardiovascular complications were reported as nonfatal or fatal and included cardiac arrest, myocardial infarction and other. A total of 50 cardiac arrests were observed during exercise, 42 of which were successfully resuscitated while eight were fatal. Seven myocardial infarctions were reported; five were nonfatal and two were fatal. Four other fatalities were reported due to acute cardiopulmonary disorders. The average complication rate for all programs was one nonfatal and one fatal event every 34,673 and 116,402 patient hours of participation, respectively. Complication rates are lower in programs which continuously monitor the electrocardiogram during exercise and are lower when only the experience since 1970 is evaluated. These data support the recommendation that medically prescribed and supervised exercise can be performed reasonably safely by medically selected cardiac patients.
THE USEFULNESS OF THE OPHTHALMOMETER.
Authors: F. C. HEATH
Journal: JAMA (1905)

The ophthalmometer has gone through various stages of appreciation, depreciation and overpraise, back and forth over the same ground again and again; and still we have its enthusiastic advocates, claiming that it does away with the necessity of using mydriatics, while others consider it as merely an expensive scientific toy, utterly unreliable and of no practical value. Is it not worth while, then, to give the subject a few minutes of dispassionate consideration? Let us first take up the question: Is the ophthalmometer of any practical use in refraction work? Those who argue against its usefulness base their argument on the ground that it only shows corneal astigmatism. The argument must turn largely, then, on the frequency and amount of lenticular astigmatism. Many authorities state that most of the astigmatism is corneal, and Suter and others explain the subtracting of half a diopter from the finding with the instrument in
Fibrin formation and degradation in patients with arteriosclerotic disease.
Authors: T Herren, H Stricker, A Haeberli, D D Do, P W Straub
Journal: Circulation (1994)

The blood coagulation cascade was reported to be activated in patients with arteriosclerotic disease of the lower limbs (peripheral arterial disease, PAD). There is more thrombin and fibrin formation compared with healthy control subjects. In many studies, however, the presence of arteriosclerotic disease had not been thoroughly ruled out in the control group. Therefore, markers of the activation of the blood coagulation cascade were measured in patients with PAD and in a carefully defined control group, both groups being subjected to an exercise test.Twenty-two patients with angiographically documented PAD of grade II (Fontaine classification) and 13 control subjects in whom the presence of arteriosclerotic lesions was ruled out by noninvasive means in the carotid arteries, abdominal aorta, leg arteries, and coronary arteries took part in the study. Before and immediately after a treadmill stress test, the concentrations of prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA; this peptide was measured in spot urine also), and D-dimers were measured. Before exercise, the concentrations of F1 + 2 (1.0 +/- 0.6 versus 0.7 +/- 0.3 nmol/L), TAT (2.9 +/- 2.1 versus 1.9 +/- 0.8 micrograms/L), and D-dimers (318.2 +/- 270.1 versus 150.0 +/- 91.4 micrograms/L) were significantly higher in the patients with PAD compared with the healthy control subjects. FPA concentrations in plasma (1.9 +/- 1.0 versus 1.4 +/- 0.6 micrograms/L) and spot urine were not different, however. F1 + 2, FPA, and D-dimer concentrations correlated with the severity of the PAD as assessed by the ankle systolic blood pressure index (ABPI). The symptom-limited stress test did not lead to further activation of the blood coagulation cascade. However, concentrations of F1 + 2 (P < .001) and TAT (P < .01) after exercise correlated with the presence of ischemic changes in the stress-test ECG.There is evidence of enhanced thrombin formation in patients with PAD compared with an age- and sex-matched control group without clinical and sonographic evidence of arteriosclerosis. The thrombin formed, however, appears to be almost completely neutralized by antithrombin III. No direct evidence of fibrin formation was obtained, since the FPA concentrations were not different. In the patients with PAD, the higher concentrations of D-dimers are indicative of in vivo fibrinolysis. Thus, some fibrin formation must be postulated to occur in patients with arteriosclerosis.
Hydrodynamic compression of the right atrium: a new echocardiographic sign of cardiac tamponade.
Authors: L D Gillam, D E Guyer, T C Gibson, M E King, J E Marshall, A E Weyman
Journal: Circulation (1983)

The relationship of right atrial inversion, a previously undescribed cross-sectional echocardiographic sign, to the presence of cardiac tamponade was examined. We studied 127 patients with moderate or large pericardial effusions. Cardiac tamponade was present in 19 and absent in 104. Four patients with equivocal tamponade were excluded from analysis. Right atrial inversion was present in 19 of 19 patients with cardiac tamponade and 19 of 104 without cardiac tamponade (sensitivity, 100%; specificity, 82%; predictive value, 50%). The degree of inversion as quantitated by the area-corrected curvature did not improve the ability to discriminate between patients with and without cardiac tamponade. However, consideration of the duration of inversion by the right atrial inversion time index (duration of inversion/cardiac cycle length) and an empirically derived cut-off of 0.34 did improve the specificity and predictive value (100% and 100%, respectively) without a significant loss of sensitivity (94%). We conclude that right atrial inversion, particularly if prolonged, is a useful echocardiographic marker of cardiac tamponade that may be of particular diagnostic value when the clinical picture is unclear.
Effect of intravenous immunoglobulin on steroid consumption in patients with severe asthma: A double-blind, placebo-controlled, randomized trial
Authors: Luis M. Salmun, Isil Barlan, Hermann M. Wolf, Martha Eibl, Frank J. Twarog, Raif S. Geha, Lynda C. Schneider
Journal: Journal of Allergy and Clinical Immunology (1999)