tbuckley/cabot-search huggingface dataset:
Single-polarity Recombinant Adeno-associated Virus 2 Vector-mediated Transgene Expression In Vitro and In Vivo: Mechanism of Transduction
Authors: Li Zhong, Xiaohuai Zhou, Yanjun Li, Keyun Qing, Xiao Xiao, Richard Jude Samulski, Arun Srivastava
Journal: Molecular Therapy (2007)

Recombinant adeno-associated virus 2 (AAV) vectors encapsidate single-stranded genomes of either polarity equally frequently in separate mature virions. Because viral genomes of either polarity are transcriptionally inactive, both the failure to undergo viral second-strand DNA synthesis and the failure to undergo DNA strand annealing have been proposed as possible reasons to account for the observed low efficiency of transgene expression. We compared the transduction efficiencies of conventional AAV vectors containing both [-] and [+] polarity genomes with those containing either the [-] or the [+] polarity genomes, in vitro as well as in vivo. We document that the transduction efficiency of single-polarity AAV vectors is significantly enhanced by (i) co-infection with adenovirus; (ii) small interfering RNA (siRNA)-mediated down-modulation of a cellular protein, FKBP52, tyrosine-phosphorylated forms of which inhibit AAV second-strand DNA synthesis; (iii) over-expression of a cellular protein tyrosine phosphatase, T cell protein tyrosine phosphatase (TC-PTP), which catalyzes tyrosine-dephosphorylation of FKBP52; and (iv) deliberate over-expression of TC-PTP, or the absence of FKBP52, respectively, in TC-PTP-transgenic mice and in FKBP52-knockout mice. These data confirm that viral second-strand DNA synthesis, rather than DNA strand annealing, is the rate-limiting step in efficient transduction by AAV vectors. This finding has implications in the use of these vectors in human gene therapy.
Lupus Erythematosus and the Antigens of the Nucleus.
Authors: W. A. Atchley
Journal: Annals of Internal Medicine (1961)

s1 May 1961Lupus Erythematosus and the Antigens of the Nucleus.W. A. Atchley, M.D., (Assoc.)W. A. Atchley, M.D., (Assoc.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1051_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe serum of patients with systemic lupus erythematosus (SLE) frequently contains antibodies which react with the isolated nucleus, fractions of the nucleus, and, less consistently, various components of the cytoplasm. This suggests but does not prove that SLE may be a disease of auto-immunity.This laboratory has developed a new and fruitful method of studying the interaction between SLE serum and biochemical fractions of the cell, with particular emphasis on material derived from the nucleus. Leukocytes obtained from patients with leukemia are washed thoroughly and extracted in dilute glycine. The extract is extremely rich in deoxyribonucleic acid (DNA) and associated... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: San Francisco, Calif. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1961Volume 54, Issue 5Page: 1051-1051KeywordsAntibodiesAntigensCytoplasmDNAGlycineLupus erythematosusResearch laboratories ePublished: 1 December 2008 Issue Published: 1 May 1961 PDF downloadLoading ...
Short wave diathermy for small spontaneous pneumothorax
Authors: Y. Ma, J. Li, Y. Liu
Journal: Thorax (1997)

BACKGROUND: The treatment of small spontaneous pneumothorax can involve observation, tube thoracostomy, and surgery. This study evaluated the use of short wave diathermy as a method of accelerating the resolution of small pneumothoraces. METHODS: Twenty two patients with pneumothoraces of less than 30% by volume were randomly allocated to receive short wave diathermy for 25 minutes each day (n = 11) or observation with bed rest (n = 11). Chest radiographs were taken until the pneumothoraces resolved. RESULTS: There were no significant differences in the clinical characteristics between the two groups of patients. However, the mean (SD) rate of absorption was significantly higher with short wave diathermy than with observation (3.44 (0.94)% versus 1.57 (0.53)%, difference = 1.87, 95% confidence interval (CI) 1.19 to 2.55, p &lt; 0.001). The time to complete reexpansion was shorter with short wave diathermy than with observation (6.86 (3.51) days versus 11.64 (3.61) days, difference = -4.78 days, 95% CI -7.95 to -1.61, p &lt; 0.005). No evidence of damage resulting from short wave diathermy was found. CONCLUSIONS: Although further study is necessary, these results indicate that short wave diathermy may be an alternative treatment for patients with small spontaneous pneumothoraces.
MITOCHONDRIA-TARGETED ANTIOXIDANT AMELIORATES DIET-INDUCED DIABETES AND DIASTOLIC DYSFUNCTION
Authors: Jaehoon Chung, Euy-Myeong Jeong, Yeongju Go, Scott Gladstein, Afshin Farzaneh-Far, E. Douglas Lewandowski, Samuel Dudley
Journal: Journal of the American College of Cardiology (2013)
Resistance to Fas-mediated apoptosis in human lung fibroblast
Authors: T. Tanaka, M. Yoshimi, T. Maeyama, N. Hagimoto, K. Kuwano, N. Hara
Journal: European Respiratory Journal (2002)

The current authors have demonstrated previously that epithelial cell apoptosis, induced by the Fas-Fas ligand pathway, might be involved in fibrosing lung diseases. Whereas lung epithelial cells are sensitive to the Fas-mediated apoptosis, lung fibroblasts may be resistant to Fas-mediated apoptosis and replace damaged epithelial cells. The WI-38 lung fibroblast cell line and primary lung fibroblasts were used to examine the resistant to Fas-mediated apoptosis and the association of anti-apoptotic proteins with this resistance. The administration of agonistic anti-Fas antibody (CH-11) or cycloheximide alone did not induce apoptosis, whereas the co-administration of CH-11 with cycloheximide induced apoptosis in WI-38 cells, in which caspase-8 and -3, but not -9, were activated, and X chromosome-linked inhibitor of apoptosis (ILP) and FLICE-like inhibitor protein (FLIP(L)), but not bcl-xL and bcl-2, were remarkably down regulated. Primary lung fibroblasts were also resistant to Fas-mediated apoptosis, and ILP and FLIP appeared to be involved in this resistance. Furthermore, the results of immunohistochemistry demonstrated that fibroblasts expressed ILP and FLIP(L) proteins in lung tissues from patients with idiopathic pulmonary fibrosis. These results suggest that anti-apoptotic proteins such as X chromosome-linked inhibitor of apoptosis and FLICE-like inhibitor protein may play an important role in preventing Fas-mediated apoptosis in lung fibroblasts, and participate in the development of pulmonary fibrosis.
Attenuation of ultraviolet <scp>A</scp> ‐induced alterations in <scp>NIH</scp> 3 <scp>T</scp> 3 dermal fibroblasts by melatonin
Authors: R. Rezzani, L.F. Rodella, G. Favero, G. Damiani, C. Paganelli, R.J. Reiter
Journal: British Journal of Dermatology (2013)

Sun exposure is responsible for long-term clinical skin changes such as photoageing, photodamage and photocancers. Ultraviolet (UV)A wavelengths stimulate the production of reactive oxygen species (ROS) that may contribute to photoageing. To protect against oxidative stress, skin cells have developed several defence systems, including ROS and metal ion scavengers and a battery of detoxifying, haem-degrading and repair enzymes. Melatonin's antioxidant activity is the result of three different but complementary actions: (i) a direct action due to its ability to act as a free radical scavenger; (ii) an indirect action that is a consequence of melatonin's ability to reduce free radical generation (radical avoidance); and (iii) its ability to upregulate antioxidant enzymes.In this study, we focused our attention on the prevention of photodamage, choosing melatonin as an antioxidant agent.In the present study we analysed the effects of pretreatment of murine fibroblasts cells (NIH3T3) with melatonin (1 mmol L(-1) ) followed by UVA irradiation (15 J cm(-2) ). Thereafter, changes in components of the extracellular matrix and in some antioxidant enzymes (inducible and constitutive haem oxygenase) were evaluated.We observed that UVA radiation caused altered expression of extracellular matrix proteins and induced the expression of inducible haem oxygenase. This increase was not sufficient to protect the cells from damage. Instead, melatonin pretreatment led to increased expression of haem-degrading enzymes and suppression of UVA-induced photodamage.These results suggest that melatonin, as a modifier of the dermatoendocrine system, may have utility in reducing the effects of skin ageing.
Differential effects of pH on calcium activation of myofilaments of adult and perinatal dog hearts. Evidence for developmental differences in thin filament regulation.
Authors: R J Solaro, P Kumar, E M Blanchard, A F Martin
Journal: Circulation Research (1986)

Our results show that calcium activation of myofilament preparations of dog heart in the perinatal period is unaffected by a reduction in pH from 7.0 to 6.5, which, in adult heart myofilaments, induces a 0.4 pCa unit (-log molar free calcium concentration) rightward shift in the relation between pCa and myofibrillar adenosine triphosphatase activity. Acidic pH also had no effect on calcium binding to myofibrillar troponin C of perinatal hearts. The stoichiometry of troponin C bound calcium at full myofilament activation (about 3 mol calcium/mol troponin C) was the same for adult and perinatal heart myofibrils, as was their myofibrillar troponin C content. Moreover, there were no differences in isoelectric pH of troponin C from adult and perinatal hearts. We tested whether variants of myofilament proteins other than troponin C could account for the differential effects of acidic pH. In adult and perinatal dog heart preparations, myosin heavy chain isoenzymes appeared the same as measured, using native pyrophosphate gel electrophoresis. No evidence for thick filament-related calcium regulation in the perinatal heart myofilaments was obtained, when tested in studies in which native thin filaments were displaced with a 10-fold molar excess of pure actin. In preparations in which native thick filaments were displaced with a 10-fold molar excess of pure skeletal muscle myosin, the effects of acidic pH on calcium activation were the same as in native adult and perinatal preparations. Our major conclusion from these results in that the perinatal heart myofilaments are likely to possess variations in thin filament activity and structure.(ABSTRACT TRUNCATED AT 250 WORDS)
THE "NEW HEEL"
Authors: MAX STRUNSKY
Journal: JAMA (1913)

The most frequent of all causes for painful feet is inflammation in the anterior arches.Of the sufferers who come for relief for foot conditions, the women patients especially\p=m-\shall we say 100 per cent. of them?\p=m-\have strained or broken-down anterior arches.It is, of course, true that in a great number of these cases the longitudinal arches are flattened also, so that there is pain in the foot due to stretching of ligaments and spasm of muscles; but still the inflammatory lesion, which is the main cause of the distressing symptoms, is situated usually in the anterior arch of the foot.I have seen a great number of cases in which the patients have worn all kinds of plates for years for their foot troubles, although their longitudinal arches were even normal\p=m-\ that is, as normal as they can be in shoe-wearing per- sons\p=m-\andof course their plates ended where the real trouble commenced, so that while the longitudinal arches were supported and treated for years, the anterior arches, in which lay the site of the lesion, were left to themselves, unrecognized and untreated.
Walking an extra 2000 steps a day reduces cardiovascular events in people at high risk of type 2 diabetes
Authors: S. Mayor
Journal: BMJ (2013)

Walking an additional 2000 steps each day reduces the risk of cardiovascular events by 8% in people with impaired glucose tolerance, shows a large international study.1

Researchers analysed prospective data concerning 9306 adults with impaired glucose tolerance and pre-existing cardiovascular disease or at least one additional cardiovascular risk factor. They were taking part in the international NAVIGATOR trial, which assessed the potential for drug treatment to reduce the onset of diabetes and cardiovascular events, but the research group also used the …
Hepatitis B Antigen in Viral Hepatitis in West London
Authors: L. J. Farrow, S. G. Lamb, N. F. Coghill, R. L. Lindon, J. Preece, A. J. Zuckerman, J. S. Stewart
Journal: BMJ (1974)

During the first 12 months of a total population survey 249 patients were seen with viral hepatitis. A total of 215 of these were tested for hepatitis B antigen (HB Ag) by radioimmunoassay and 32 (15%) were positive. More than five times as many men (27) as women (5) were HBAg positive and 19 of the men were between the ages of 20 and 39 years. There were only four drug addicts among those tested, two of whom were positive, as were two of the four patients who were tattooed. Sixty out of 86 children (under 15 years) were tested for HBAg and none was positive.
A plain man's guide to maintenance.
Authors: P Lawrance
Journal: BMJ (1984)

Hospitals house a variety of equipment, and it would be inappropriate in this article to give detailed maintenance schedules for any particular items. Instead, I intend to try to present a practical approach from my own experience of maintaining and repairing equipment in developing countries. As a general principle it is wise to adhere to the manufacturer's recommendations whenever possible, but this is a counsel of perfection that is seldom easy to follow because of lack of information, spare parts, or, simply, time.
THE ANALOGY BETWEEN ACUTE IDIOPATHIC PLEURITIS AND ACUTE ARTICULAR RHEUMATISM.
Authors: E. L. SHURLY
Journal: JAMA (1892)

In the year 1887, I read a paper bearing the above title before the Michigan State Medical Society, which at the time attracted very little attention. However, subsequent observation of these diseases has led me to think that too little importance has been placed upon this question; and for this reason, I venture now to bring the matter again to public notice. Attention was first called to this relationship by Vallieux in 1854, and afterwards by Davis, of London, England; but without awakening much thought at that time or subsequently. In the paper alluded to, the theoretical basis assumed of the identity of the two diseases was mainly twofold, on the one hand histological, because the pleura as well as the synovial and other serous membranes spring from the same primordial layer, the meso-blast or middle layer, and ultimately develop into the endothelial layer which is the lining of all
Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo
Authors: Mark Stroh, John P Zimmer, Dan G Duda, Tatyana S Levchenko, Kenneth S Cohen, Edward B Brown, David T Scadden, Vladimir P Torchilin, Moungi G Bawendi, Dai Fukumura, Rakesh K Jain
Journal: Nature Medicine (2005)
CpG island methylator phenotypes in aging and cancer
Authors: Minoru Toyota, Jean-Pierre J. Issa
Journal: Seminars in Cancer Biology (1999)

CpG islands are short stretches of CpG rich regions that are frequently associated with the promoter region of genes. Aberrant methylation of CpG islands is one mechanism of inactivating tumor suppressor genes (TSGs) in neoplasia, and there is growing evidence that altered cytosine methylabtion play important roles in cancer development. However, the differences in global CpG island methylation patterns between normal and cancer cells remain poorly understood. By examining a large number of loci in a series of cancers, global methylation profiles can be constructed. Such studies revealed that in colorectal cancer, there appears to be two types of methylation that are associated with cancer progression: type A (for age-related) methylation, and type C (for cancer-specific) methylation. Initially, type A methylation arises as a function of age in normal colorectal epithelial cells. By affecting genes that regulate the growth and/or differentiation of these cells, such methylation may result in a predisposition state that precedes tumor formation in the colon. Type C methylation, by contrast, was found exclusively in a subset of cancers, which display a CpG island methylator phenotype (CIMP). CIMP is a novel molecular instability pathway that appears to be responsible for most cases of aberrant TSG methylation in colorectal cancer, and which has important interactions with genetic pathways as well. In fact, CIMP+ tumors account for the majority of sporadic colorectal cancers with microsatellite instability, through methylation of the mismatch repair gene hMLH1. This model whereby age-related methylation increases cell-susceptibility to transformation and cancer-specific methylabtion results in neoplastic progression in a subset of cases may be applicable to many human neoplasms.
ZAP‐70 expression is associated with increased risk of autoimmune cytopenias in CLL patients
Authors: Roberta Zanotti, Franzesco Frattini, Paolo Ghia, Carlo Visco, Alberto Zamò, Omar Perbellini, Stefania Stella, Monica Facco, Ilaria Giaretta, Marco Chilosi, Giovanni Pizzolo, Achille Ambrosetti
Journal: American Journal of Hematology (2010)

Autoimmune cytopenias (AIC) are frequent in chronic lymphocytic leukemia (CLL) patients, but risk factors and prognostic relevance of these events are controversial. Data about the influence on AIC of biological prognostic markers, as ZAP-70, are scanty. We retrospectively evaluated AIC in 290 CLL patients tested for ZAP-70 expression by immunohistochemistry on bone marrow biopsy at presentation. They were 185 men, median age 63 years, 77.9% Binet stage A, 17.6% B and 4.5% C. AIC occurred in 46 patients (16%): 31 autoimmune hemolytic anemias, 10 autoimmune thrombocytopenias, four Evans syndromes, and one pure red cell aplasia. Of the 46 cases of AIC, 37 (80%) occurred in ZAP-70 positive patients and nine (20%) in ZAP-70 negatives. ZAP-70 expression [Hazard Ratio (HR) = 7.42; 95% confidence interval (CI): 2.49-22.05] and age >65 years (HR = 5.41; 95% CI: 1.67-17.49) resulted independent risk factors for AIC. Among the 136 patients evaluated both for ZAP-70 expression and IGHV status, the occurrence of AIC was higher in ZAP-70 positive/IGHV unmutated cases (35%) than in patients ZAP-70 negative/IGHV mutated (6%) or discordant for the two parameters (4%; P < 0.0001). In ZAP-70 positive patients, occurrence of AIC negatively influenced survival (HR = 1.75; 95% CI: 1.06-2.86). The high risk of developing AIC in ZAP-70 positive CLL, particularly when IGHV unmutated, should be considered in the clinical management.
Renal Transplantation: Theory and Practice
Authors: Richard E. Wilson
Journal: JAMA (1972)

This concise yet thorough review of renal transplantation has been written by one of the most prestigious transplant groups in the world. Professor Hamburger and his colleagues at Hôpital Necker in Paris were one of the very first groups to begin renal transplantation and have maintained an active interest in both experimental aspects of transplantation immunology and clinical renal transplant programs ever since. This book is essentially split in half between experimental aspects of transplantation biology and immunology on the one hand, and clinical techniques and results of renal transplantation on the other. There is also an extensive appendix of 56 pages which outlines in greater detail the surgical and immunological techniques involved in both the clinical and experimental aspects. Each chapter has many subsections, identified in the table of contents and at the beginning of each chapter, so that the reader can quickly identify specific points of interest. An
THU0038 Abnormal Phenotypic T Cell Subsets in Peripheral Blood of Tunisian Patients with Behcet’s Disease
Authors: K. Sakly, C. Lambert, M. Maatouk, S. Hammami, N. Sakly, O. Harzallah, F. Nefzi, S. Mahjoub, I. Ghedira, S. Feki
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Behçet’s disease (BD) is a chronic recurrent multisystemic inflammatory disorder of unknown origin. Immune-mediated mechanisms play a major role in the pathogenesis of the disease. BD is not considered to be an autoimmune disorder, and the character of the disease needs to be clarified [1]. <h3>Objectives</h3> The aim of this study was to determine the immunophenotypic profile of T cell subsets in patients with BD. <h3>Methods</h3> 30 patients with BD, 19 males and 11 females (mean age: 39.65±10.7 years) were enrolled in this study. They are constituted of 20 patients with inactive cases and 10 patients with active cases. Eight volunteer donors were recruited as healthy controls (HC) (mean age: 32.8±13.6 years). The following monoclonal antibody combination was used to characterize the phenotypes of T cells: anti-CD4-Chrome orange/anti-CD3-PacificBlue/anti-CD62L-PE/anti-CD127-APC-Cy7/anti-CD25-PerCP-Cy5/anti-CD45RA-PCy7 and anti-CD8-APC. Analysis was performed on a FACSDiva flow cytometer using FACSDiva™ software. <h3>Results</h3> Our study showed that patients with BD, as compared with HC, had significantly decreased percentage of CD25brightCD127- CD4+ Treg cells (3.38 ± 1.7% versus 4.8 ± 0.26%; P = 0.039), significantly reduced percentage of CD45RA+CD62L+CD4+ naïve T cells (8.16 ± 6.34% versus 26.7 ± 6.4%; P = 0.001) and increased percentage of CD45RA–CD62L– CD4+ effector memory T cells (56.41 ± 19.5% versus 32.07 ± 8.5%; P = 0.04). However, no differences were found between patients and HC regarding T CD8+ cell subsets. On the other hand, patients with active BD showed, in comparison to patients in remission, decreased percentages of CD45RA+CD62L+CD4+ naïve T cells (4.19 ± 3.1% versus 11.25 ± 6.42%; P = 0.02) and terminally differentiated CD45RA+CD62L-CD4+ effector memory T cells (9.29 ±3.6% versus 18.97 ± 11.34%; P = 0.013) but increased percentages of CD4+CD45RA-CD62L- effectors memory T cells (70.61± 11.82% versus 48.78 ± 17%; P = 0.005). Moreover, patients with active BD are characterized by significantly decreased CD45RA+CD62L+CD8+ naïve T cells compared to patients in remission (6.49±4% versus 13.87±6.8%; P=0.017) and a significantly increased percentage of CD45RA–CD62L–CD8+ effectors memory T cells (63.89±13.4% versus 44.36±11.9%; P=0.004). <h3>Conclusions</h3> Our study showed that patients with BD are characterized by decreased percentages of T regs and increased percentages of effector memory T cells. The latter subset of T cells is also increased in active BD. The understanding of these findings could contribute to the clarification of the role of these cell subsets in the pathogenesis of BD and disease activity. <h3>References</h3> Kapsimali, V.D., et al., Etiopathogenesis of Behcet’s disease with emphasis on the role of immunological aberrations. Clin Rheumatol, 2010. 29(11): p. 1211-6. <h3>Disclosure of Interest</h3> None Declared