tbuckley/cabot-search huggingface dataset:
Single-Dose Oritavancin in the Treatment of Acute Bacterial Skin Infections
Authors: G. Ralph Corey, Heidi Kabler, Purvi Mehra, Sandeep Gupta, J. Scott Overcash, Ashwin Porwal, Philip Giordano, Christopher Lucasti, Antonio Perez, Samantha Good, Hai Jiang, Greg Moeck, William O'Riordan
Journal: New England Journal of Medicine (2014)

Oritavancin is a lipoglycopeptide with bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and prolonged half-life allow for single-dose treatment.We conducted a randomized, double-blind trial in which adults with acute bacterial skin and skin-structure infections received either a single intravenous dose of 1200 mg of oritavancin or a regimen of intravenous vancomycin twice daily for 7 to 10 days. Three efficacy end points were tested for noninferiority. The primary composite end point was defined as cessation of spreading or reduction in lesion size, absence of fever, and no need for administration of a rescue antibiotic 48 to 72 hours after administration of oritavancin. Secondary end points were clinical cure 7 to 14 days after the end of treatment, as determined by a study investigator, and a reduction in lesion size of 20% or more 48 to 72 hours after administration of oritavancin.The modified intention-to-treat population comprised 475 patients who received oritavancin and 479 patients who received vancomycin. All three efficacy end points met the prespecified noninferiority margin of 10 percentage points for oritavancin versus vancomycin: primary end point, 82.3% versus 78.9% (95% confidence interval [CI] for the difference, -1.6 to 8.4 percentage points); investigator-assessed clinical cure, 79.6% versus 80.0% (95% CI for the difference, -5.5 to 4.7 percentage points); and proportion of patients with a reduction in lesion area of 20% or more, 86.9% versus 82.9% (95% CI for the difference, -0.5 to 8.6 percentage points). Efficacy outcomes measured according to type of pathogen, including methicillin-resistant Staphylococcus aureus, were similar in the two treatment groups. The overall frequency of adverse events was also similar, although nausea was more common among those treated with oritavancin.A single dose of oritavancin was noninferior to twice-daily vancomycin administered for 7 to 10 days for the treatment of acute bacterial skin and skin-structure infections caused by gram-positive pathogens. (Funded by the Medicines Company; SOLO I ClinicalTrials.gov number, NCT01252719.).
PEGylation of HPMA-based block copolymers enhances tumor accumulation in vivo : A quantitative study using radiolabeling and positron emission tomography
Authors: Mareli Allmeroth, Dorothea Moderegger, Daniel Gündel, Hans-Georg Buchholz, Nicole Mohr, Kaloian Koynov, Frank Rösch, Oliver Thews, Rudolf Zentel
Journal: Journal of Controlled Release (2013)
Discrete Shoot and Root Stem Cell-Promoting WUS/WOX5 Functions Are an Evolutionary Innovation of Angiosperms
Authors: Judith Nardmann, Pascal Reisewitz, Wolfgang Werr
Journal: Molecular Biology and Evolution (2009)

The morphologically diverse bodies of seed plants comprising gymnosperms and angiosperms, which separated some 350 Ma, grow by the activity of meristems containing stem cell niches. In the dicot model Arabidopsis thaliana, these are maintained by the stem cell-promoting functions of WUS and WUSCHEL-related homeobox 5 (WOX5) in the shoot and the root, respectively. Both genes are members of the WOX gene family, which has a monophyletic origin in green algae. The establishment of the WOX gene phylogeny from basal land plants through gymnosperms to basal and higher angiosperms reveals three major branches: a basal clade consisting of WOX13-related genes present in some green algae and throughout all land plant genomes, a second clade containing WOX8/9/11/12 homologues, and a modern clade restricted to seed plants. The analysis of the origin of the modern branch in two basal angiosperms (Amborella trichopoda and Nymphaea jamesoniana) and three gymnosperms (Pinus sylvestris, Ginkgo biloba, and Gnetum gnemon) shows that all members of the modern clade consistently found in monocots and dicots exist at the base of the angiosperm lineage, including WUS and WOX5 orthologues. In contrast, our analyses identify a single WUS/WOX5 homologue in all three gymnosperm genomes, consistent with a monophyletic origin in the last common ancestor of gymnosperms and angiosperms. Phylogenetic data, WUS- and WOX5-specific evolutionary signatures, as well as the expression pattern and stem cell-promoting function of the single gymnosperm WUS/WOX5 pro-orthologue in Arabidopsis indicate a gene duplication event followed by subfunctionalization at the base of angiosperms.
Platelet-rich plasma: any substance into it?
Authors: O Mei-Dan, G Mann, N Maffulli
Journal: British Journal of Sports Medicine (2010)

The recognition of the 17q21.31 microdeletion syndrome has been facilitated by high-resolution microarray technology. Recent clinical delineation of this condition emphasises a typical facial appearance, cardiac and renal defects, and speech delay in addition to intellectual disability, hypotonia and seizures. We describe eleven previously unreported patients expanding the phenotypic spectrum to include aortic root dilatation, recurrent joint subluxation, conductive hearing loss due to chronic otitis media, dental anomalies and persistence of fetal fingertip pads. Molecular analysis of the deletions demonstrates a critical region spanning 440 kb involving either partially or wholly five genes, CRHR1, IMP5, MAPT, STH and KIAA1267. These data have significant implications for the clinical diagnosis and management of other individuals with 17q21.31 deletions.
Sensitivity of quantitative 1H magnetic resonance spectroscopy of the brain in detecting early neuronal damage in systemic lupus erythematosus
Authors: J S Axford
Journal: Annals of the Rheumatic Diseases (2001)

To quantify N-acetylaspartate (NAA), total creatines (tCr), total cholines (tCho), and myo-inositol (mI) levels in normal and abnormal appearing white matter of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) in order to determine the specific changes in metabolite concentrations.Axial proton density and T(2) weighted magnetic resonance images, and short echo time (TE 30 ms) (1)H spectra were acquired with a GE SIGNA 1.5 T magnetic resonance system. Concentrations of NAA, tCr, tCho, and mI were determined, using brain tissue water as a reference, from nine patients (seven female, mean age 40.3 years, range 16-65) with NPSLE and eight healthy women (mean age 43 years, range 31-65).A significant rise of tCho (12.4%, p<0.05) and mI (31.4%, p<0.005) and a significant reduction in NAA (-12%, p<0.05) was found in normal appearing white matter compared with controls. Analysis according to severity of the clinical NPSLE features (subgrouped as major or minor) showed that SLE major had reduced NAA compared with SLE minor (-18.4%, p<0.05) and controls (-20%, p<0.005). The SLE major group showed a significant rise of mI (32%, p<0.01) and the SLE minor group a significant increase in tCho (18.6%, p<0.05) compared with controls. Longitudinal analysis of brain metabolites in normal appearing white matter showed consistent abnormalities in NAA, tCho, and mI in a patient with stable clinical features and a constant rise of tCho, but transient rise of mI was seen during a flare of disease in another patient.Quantitative (1)H magnetic resonance spectroscopy (MRS) suggests a particular course of neurometabolite changes that precedes irreversible reductions in NAA and permanent neuronal loss. Initially, in patients with SLE minor, there is a significant rise in tCho and a trend (reversible) for mI also to be raised. In patients with SLE major the NAA is significantly and permanently reduced and mI is significantly raised, whereas the tCho levels are near normal. Further investigations are needed to determine how specific MRS is as a clinical marker for brain disturbance in SLE.
ZAP-70 Expression in Normal Pro/Pre B Cells, Mature B Cells, and in B-Cell Acute Lymphoblastic Leukemia
Authors: Marta Crespo, Neus Villamor, Eva Giné, Ana Muntañola, Dolors Colomer, Teresa Marafioti, Margaret Jones, Mireia Camós, Elias Campo, Emili Montserrat, Francesc Bosch
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The ZAP-70 gene is normally expressed in T and natural killer cells, where it is required for the T-cell receptor (TCR) signaling. More recently, it has been described that ZAP-70 contributes to the B-cell development at early stages of B-cell differentiation in mice. The purpose was to investigate the presence of ZAP-70 in normal pro/pre B cells and mature B cells and in tumoral cells from B-acute lymphoblastic leukemias (B-ALL). Experimental Design: ZAP-70 expression was ascertained by flow cytometry, immunofluorescence, Western blot, and quantitative reverse transcription-PCR. Analysis of ZAP-70 and other signaling proteins of the pre-TCR/TCR was done by Western blot. Results: ZAP-70 was expressed in pro/pre B cells but not in normal mature B cells derived from bone marrow, peripheral blood, or tonsil. Among tumoral cells, ZAP-70 was expressed in 56% of B-ALLs with pro/pre B-cell phenotype and in 4 of 6 Burkitt/ALL lymphomas. In B-ALL cells, expression of CD38 protein correlated with ZAP-70 expression (P = 0.05). Mutational analysis of the ZAP-70 gene revealed the absence of mutations in cases lacking ZAP-70 expression. Moreover, other elements of the pre-TCR/TCR signaling pathway, like LAT and Lck, were also found in B-ALL cells. Conclusions: Among normal B-cell subsets, ZAP-70 was found expressed in normal pro/pre B cells but not in a significant proportion of normal B cells with mature phenotype. Moreover, the presence of ZAP-70 in B-ALLs probably reflects their cellular origin. The lack of ZAP-70 expression in normal mature B cells suggests that its expression in mature-derived neoplasms with different cellular origin, such as Burkitt's lymphoma and chronic lymphocytic leukemia, might be due to an aberrant phenomenon.
Immunohistochemical Evidence for an Increased Oxidative Stress and Carbonyl Modification of Proteins in Diabetic Glomerular Lesions
Authors: DAISUKE SUZUKI, TOSHIO MIYATA, NOBORU SAOTOME, KATSUNORI HORIE, REIKO INAGI, YOSHINARI YASUDA, KOJI UCHIDA, YUKO IZUHARA, MITSUNORI YAGAME, HIDETO SAKAI, KIYOSHI KUROKAWA
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Advanced glycation end products (AGE) include a variety of protein adducts whose accumulation has been implicated in tissue damage associated with diabetic nephropathy (DN). It was recently demonstrated that among AGE, glycoxidation products, whose formation is closely linked to oxidation, such as carboxymethyllysine (CML) and pentosidine, accumulate in expanded mesangial matrix and nodular lesions in DN, in colocalization with malondialdehyde-lysine (MDA-lysine), a lipoxidation product, whereas pyrraline, another AGE structure whose deposition is rather independent from oxidative stress, was not found within diabetic glomeruli. Because CML, pentosidine, and MDA-lysine are all formed under oxidative stress by carbonyl amine chemistry between protein amino group and carbonyl compounds, their colocalization suggests a local oxidative stress and increased protein carbonyl modification in diabetic glomerular lesions. To address this hypothesis, human renal tissues from patients with DN or IgA nephropathy were examined with specific antibodies to characterize most, if not all, carbonyl modifications of proteins by autoxidation products of carbohydrates, lipids, and amino acids: CML (derived from carbohydrates, lipids, and amino acid), pentosidine (derived from carbohydrates), MDA-lysine (derived from lipids), 4-hydroxynonenal-protein adduct (derived from lipids), and acrolein-protein adduct (derived from lipids and amino acid). All of the protein adducts were identified in expanded mesangial matrix and nodular lesions in DN. In IgA nephropathy, another primary glomerular disease leading to end-stage renal failure, despite positive staining for MDA-lysine and 4-hydroxynonenal-protein adduct in the expanded mesangial area, CML, pentosidine, and acrolein-protein adduct immunoreactivities were only faint in glomeruli. These data suggest a broad derangement in nonenzymatic biochemistry in diabetic glomerular lesions, and implicate an increased local oxidative stress and carbonyl modification of proteins in diabetic glomerular tissue damage (“carbonyl stress”).
India cancels trade talks after Europe bans 700 generic drugs
Authors: Vidya Krishnan
Journal: BMJ (2015)

India’s government has cancelled a meeting with the European Union’s chief trade negotiator, due later this month, after the EU imposed an import ban on 700 generic drugs made by the company GVK Biosciences, which provides clinical trial services to many manufacturers of generic drugs across the country. The move is being seen as a serious blow to the proposed free trade agreement between the EU and India.

Negotiations over the agreement were scheduled to begin again at the end of the month after a two year break, with a meeting planned for 28 August between India’s chief trade negotiator, J S Deepak, and his EU counterpart, Ignacio Garcia Bercero.

However, the meeting was abruptly cancelled, and the Indian commerce ministry said in a written statement that it was “disappointed and concerned by …
Stunned myocardium?an unfinished puzzle
Authors: F EBERLI
Journal: Cardiovascular Research (2004)

Journal Article Stunned myocardium—an unfinished puzzle Get access Franz R Eberli Franz R Eberli * Cardiovascular Center, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland *Tel.: +41-1-255-33-97, +41-1-255-22-16; fax: +411-255-44-01. Email address: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 63, Issue 2, August 2004, Pages 189–191, https://doi.org/10.1016/j.cardiores.2004.06.008 Published: 01 August 2004 Article history Received: 07 June 2004 Accepted: 09 June 2004 Published: 01 August 2004
Induction of in vitro proliferation and maturation of human aneuploid myelogenous leukemic cells.
Authors: J W Chiao, M Andreeff, W B Freitag, Z Arlin
Journal: The Journal of Experimental Medicine (1982)

Human leukemic cells were induced to proliferate and mature to macrophage-like cells in primary cultures supplemented with conditioned medium (CM) from phytohemagglutinin and alloantigen-stimulated normal T lymphocytes. Blast and promyelocyte-enriched preparations, isolated after depletion of adherent phagocytic cells and lymphoid cells from samples of myelogenous leukemia patients, were suspended in liquid cultures with 30% CM. Cell cycle analysis was performed throughout the course of induced cellular maturation. Within 24 h of exposure to CM, cells with macrophage-like morphology were identified among the developing adherent cells. Approximately 15-30% of the cells in culture suspensions also developed macrophage-like morphology and esterase reactivity with alpha-napthyl acetate after incubation for 2 d. The number of these nonproliferating cells increased and became predominant in the later culture period. Flow cytometric measurement of DNA content showed that these mature cells had the same aneuploid stemline as the undifferentiated leukemic cells, indicating that genetically abnormal leukemic cells can be induced to differentiate. Reduction in the total RNA content of the macrophage-like cells was also determined by flow cytometry. Reduction in RNA and development of adherent cells served as early markers of maturation, in addition to the later acquisition of complement receptors and phagocytic capacity. Cell cycle analysis showed that CM stimulated the proliferation of immature cells. This initial proliferation may precede intertwined events of proliferation and concurrent maturation of immature cells. Later in the culture period, cellular proliferation decreased, leading to termination of the cultures.
TRANSEPIDERMAL WATER LOSS IN PATIENTS WITH DERMATITIS
Authors: M. SHAHIDULLAG, E. J. RAFFLE, W. FRAIN-BELL
Journal: British Journal of Dermatology (1969)

Journal Article TRANSEPIDERMAL WATER LOSS IN PATIENTS WITH DERMATITIS Get access M. SHAHIDULLAG, M. SHAHIDULLAG Department of Dermatology, The University, Dundee, and Regional Physics Department, Dundee Search for other works by this author on: Oxford Academic Google Scholar E. J. RAFFLE, E. J. RAFFLE Department of Dermatology, The University, Dundee, and Regional Physics Department, Dundee Search for other works by this author on: Oxford Academic Google Scholar W. FRAIN‐BELL W. FRAIN‐BELL Department of Dermatology, The University, Dundee, and Regional Physics Department, Dundee Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 10, 1 October 1969, Pages 722–730, https://doi.org/10.1111/j.1365-2133.1969.tb15931.x Published: 01 October 1969 Article history Accepted: 22 February 1969 Published: 01 October 1969
Plasma Folate Levels and Risk of Spontaneous Abortion
Authors: Lena George, James L Mills, Anna L V Johansson, Anna Nordmark, Bodil Olander, Fredrik Granath, Sven Cnattingius
Journal: JAMA (2002)

Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies.To study the association between plasma folate levels and the risk of spontaneous abortion.Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks.Risk of spontaneous abortion vs maternal plasma folate level.Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low (< or =2.19 ng/mL [< or =4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and > or =6.17 ng/mL [> or =14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% CI, 0.59-1.20; and OR, 0.74; 95% CI, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% CI, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% CI, 0.55-2.24) or unknown (OR, 1.45; 95% CI, 0.90-2.33).Low plasma folate levels were associated with an increased risk of early spontaneous abortion.
Reregistration of medical specialists in the Netherlands
Authors: J A Swinkels
Journal: BMJ (1999)

Since 1991 all specialists in the Netherlands have had to get reregistered every five years in order to retain their place on the medical register.Although the criteria for reregistration were initially solely quantitative, being based on a minimum number of hours spent in specialist practice, qualitative criteria have now been introduced.A new law which is expected to come into force in January 2000 requires doctors to complete 40 hours a year of accredited continuing medical education or to be assessed in the workplace every five years.In practice, however, most specialist societies are requiring their members to fulfil both of these requirements in order to reregister. MethodsThis article is based on my experience as chairman of the committee of quality of care and member of the council on quality, science, and education of the Dutch Association of Medical Specialists (Orde van Medisch Specialisten) and on key references relating to quality management. 1 2 Further information was obtained through a net search (www.artsen.net).
Role of αvβ6 integrin in acute biliary fibrosis
Authors: Bruce Wang, Brian M. Dolinski, Noriko Kikuchi, Diane R. Leone, Marion G. Peters, Paul H. Weinreb, Shelia M. Violette, Montgomery D. Bissell
Journal: Hepatology (2007)

Acute biliary obstruction leads to periductal myofibroblasts and fibrosis, the origin of which is uncertain. Our study provides new information on this question in mice and humans. We show that bile duct obstruction induces a striking increase in cholangiocyte αvβ6 integrin and that expression of this integrin is directly linked to fibrogenesis through activation of transforming growth factor beta (TGF-β). Administration of blocking antibody to αvβ6 significantly reduces the extent of acute fibrosis after bile duct ligation. Moreover, in β6-null mice subjected to the injury, fibrosis is reduced by 50% relative to that seen in wild-type mice, whereas inflammation occurs to the same extent. The data indicate that αvβ6, rather than inflammation, is linked to fibrogenesis. It is known that αvβ6 binds latent TGF-β and that binding results in release of active TGFβ. Consistent with this, intracellular signaling from the TGFβ receptor is increased after bile duct ligation in wild-type mice but not in β6−/− mice, and a competitive inhibitor of the TGFβ receptor type II blocks fibrosis to the same extent as antibody to αvβ6. In a survey of human liver disease, expression of αvβ6 is increased in acute, but not chronic, biliary injury and is localized to cholangiocyte-like cells. Conclusion : Cholangiocytes respond to acute bile duct obstruction with markedly increased expression of αvβ6 integrin, which is closely linked to periductal fibrogenesis. The findings provide a rationale for the use of inhibitors of αvβ6 integrin or TGFβ for down-regulating fibrosis in the setting of acute or ongoing biliary injury.
Protamine Sulfate Inhibition of Serum-Induced Mitogenic Responses: Differential Effects on Normal and Neoplastic Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Samuel J. Leibovich, Peter J. Polverini
Journal: JNCI Journal of the National Cancer Institute (1984)

Protamine sulfate reversibly inhibits serum-induced mitogenic stimulation of several nontransformed and neoplastic cell types in vitro. Fifty percent inhibition was induced by approximately 120-150 micrograms protamine sulfate/ml. Cells were affected directly, and inhibition depended on the duration of cell exposure. Heparin, chondroitin sulfate, heparan sulfate, and dextran sulfate neutralized protamine sulfate effects during the early stages of treatment. Nontransformed cells [bovine aortic endothelial cells, adult human gingival fibroblasts (strains 423 and 1101), fetal rat skin (strain 921-K) and muscle fibroblasts] required longer exposure to induce inhibition than did neoplastic cells [rat 3-methylcholanthrene-induced fibrosarcoma cell lines (MCA-6 and MCA-9), a macrophage-like cell line (NCTC-3749), Walker 256 rat carcinoma cells (ATCC-CCL-38), rat Morris hepatoma cells (ATCC-CCL-144), murine melanoma cells (B16), and rat bladder squamous cell carcinoma cells (804-G)]. Other polycationic compounds, including histone type VIII-S, poly-L-lysine, poly-L-arginine, and protamine (free base), were also effective inhibitors, whereas the basic proteins cytochrome c and lysozyme had no effect. Poly-L-histidine, poly-L-glutamic acid, poly-L-aspartic acid, and dextran blue also had no inhibitory effect.