gebhart/patrepeval huggingface dataset:
Preclinical Testing Oncolytic Vaccinia Virus Strain GLV-5b451 Expressing an Anti-VEGF Single-Chain Antibody for Canine Cancer Therapy (2015)

Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is a novel approach for canine cancer therapy. Here we describe, for the first time, the characterization and the use of VACV strain GLV-5b451 expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as therapeutic agent against different canine cancers. Cell culture data demonstrated that GLV-5b451 efficiently infected and destroyed all four tested canine cancer cell lines including: mammary carcinoma (MTH52c), mammary adenoma (ZMTH3), prostate carcinoma (CT1258), and soft tissue sarcoma (STSA-1). The GLV-5b451 virus-mediated production of GLAF-2 antibody was observed in all four cancer cell lines. In addition, this antibody specifically recognized canine VEGF. Finally, in canine soft tissue sarcoma (CSTS) xenografted mice, a single systemic administration of GLV-5b451 was found to be safe and led to anti-tumor effects resulting in the significant reduction and substantial long-term inhibition of tumor growth. A CD31-based immuno-staining showed significantly decreased neo-angiogenesis in GLV-5b451-treated tumors compared to the controls. In summary, these findings indicate that GLV-5b451 has potential for use as a therapeutic agent in the treatment of CSTS.
The Role of Biotin-Dependent Pyruvate Carboxylase inl-Lysine Production (1979)

The promotive effect of biotin (200~500 µg/liter) on l-lysine formation was investigated in Brevibacterium lactofermentum. This effect was observed only when glucose or pyruvate was used as sole carbon source, and accompanied with the specific incorporation of 18CO2 into γ-CH2 group of l-lysine. Brev. lactofermentum AJ 3445 (AECr) could grow on pyruvate medium supplemented with biotin at more than 200 µg/liter, while the same growth was observed with the addition of TCA cycle members or glutamate to pyruvate medium. Phosphoenolpyruvate (PEP) carboxylase deficient mutant derived from AJ 3445 could not grow on glucose as sole carbon source, but on glucose plus 200 µg/liter of biotin. AJ 3445 grown on lactate medium containing 500 µg/liter of biotin and KHCO3 contained the biotin-dependent pyruvate carboxylase. These data suggest that this promotive effect of excess biotin on l-lysine formation may be brought about through the activation of pyruvate carboxylase by biotin.
Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance (1997)

Receptor subunits for the neurocytokine ciliary neurotrophic factor (CNTF) share sequence similarity with the receptor for leptin, an adipocyte-derived cytokine involved in body weight homeostasis. We report here that CNTF and leptin activate a similar pattern of STAT factors in neuronal cells, and that mRNAs for CNTF receptor subunits, similarly to the mRNA of leptin receptor, are localized in mouse hypothalamic nuclei involved in the regulation of energy balance. Systemic administration of CNTF or leptin led to rapid induction of the tis-11 primary response gene in the arcuate nucleus, suggesting that both cytokines can signal to hypothalamic satiety centers. Consistent with this idea, CNTF treatment of ob/ob mice, which lack functional leptin, was found to reduce the adiposity, hyperphagia, and hyperinsulinemia associated with leptin deficiency. Unlike leptin, CNTF also reduced obesity-related phenotypes in db/db mice, which lack functional leptin receptor, and in mice with diet-induced obesity, which are partially resistant to the actions of leptin. The identification of a cytokine-mediated anti-obesity mechanism that acts independently of the leptin system may help to develop strategies for the treatment of obesity associated with leptin resistance.
Medical image registration (2001)

Radiological images are increasingly being used in healthcare and medical research. There is, consequently, widespread interest in accurately relating information in the different images for diagnosis, treatment and basic science. This article reviews registration techniques used to solve this problem, and describes the wide variety of applications to which these techniques are applied. Applications of image registration include combining images of the same subject from different modalities, aligning temporal sequences of images to compensate for motion of the subject between scans, image guidance during interventions and aligning images from multiple subjects in cohort studies. Current registration algorithms can, in many cases, automatically register images that are related by a rigid body transformation (i.e. where tissue deformation can be ignored). There has also been substantial progress in non-rigid registration algorithms that can compensate for tissue deformation, or align images from different subjects. Nevertheless many registration problems remain unsolved, and this is likely to continue to be an active field of research in the future.
Geological Landforms and Its Utilization of Travel Resources in Rizhao City (2007)

Geological landforms are very rich in Rizhao city,which are major parts of travel resources.Geological landfoms in inland are mountains,rivers and manual lakes,and in coastal areas are brig,skerry,coast and barachois.It is put forward that geological landforms should be used scientifically, ecological environment should be protected and formal geological landforms should be kept as well.
Activation of reconstituted Escherichia coli outer‐membrane phospholipase A by membrane‐perturbing peptides results in an increased reactivity towards the affinity label hexadecanesulfonyl fluoride (1991)

The activity of the Escherichia coli outer-membrane phospholipase (OM PLA) is strictly regulated in its natural habitat, the E. coli outer membrane. OM PLA can be reconstituted in phospholipid bilayers, resulting in low specific activity of the enzyme compared to its activity on mixed lipid/detergent micelles. The enzyme can be activated by the addition to these vesicles of the membrane-perturbing peptides polymyxin B, melittin or cardiotoxin resulting in hydrolysis of mainly the sn-1 ester bond of the phospholipids as is also observed in vivo. We used the affinity label hexadecanesulfonyl fluoride to probe the influence of lipid environment on the activity of OM PLA. In detergent and substrate micelles, the rate constant for the sulfonylation of the active-center serine of the purified OM PLA by the affinity label hexadecanesulfonyl fluoride depends on amphiphile concentration. We have reported a similar influence of amphiphile concentration on the activity of the enzyme [Horrevoets, A. J. G. et al. (1989) Biochemistry 28, 1139-1147]. Analysis of the rates of inactivation of OM PLA by hexadecanesulfonyl fluoride in vesicles composed of various phospholipids indicated that activation of the enzyme by membrane-perturbing peptides can be accurately quantified with this affinity label. Our results show that the affinity label hexadecanesulfonyl fluoride can be used to monitor the state of activation of OM PLA in different lipid environments, including non-hydrolyzable substrate analogues. Implications for the in vivo situation are discussed.
Cell lines (2012)

Cell lines are often used in place of primary cells to study biological processes. However, care must be taken when interpreting the results as cell lines do not always accurately replicate the primary cells. In this article, we will briefly talk about advantages and disadvantages of cell lines and then discuss results using the mouse Sertoli cell line, MSC-1, compared with primary mouse Sertoli cells. MSC-1 cells resemble Sertoli cells morphologically and possess several biochemical markers associated with Sertoli cells. Studies have demonstrated that the function and regulation of retinoic acid receptor α (RARα) is similar between MSC-1 and rat Sertoli cells. However, MSC-1 cells lack some of the immune privilege properties associated with primary Sertoli cells, including survival in animals with a fully functional immune system. Therefore, it has to be kept in mind that cell lines do not behave identically with primary cells and should not be used to replace primary cells. In order to strengthen the findings, key control experiments using primary cells should always be performed.
GM3(Hematoside) Sphingolipodystrophy (1974)

To characterize further disorders involving storage of glycosphingolipids, we studied an infant who had poor physical and motor development, coarse facies, macroglossia, gingival hypertrophy, squat hands and feet, flexor contractures of the fingers, thickened, loose, hirsute skin, bilateral large inguinal hernias, an enlarged liver and spleen, and normal fundi. Shortly after birth the patient became limp and unresponsive, dying at 3 1/2 months of age. The accumulation of ganglioside GM3 (hematoside) was established by quantitative lipid analysis of fresh-frozen post-mortem samples of brain and liver. Higher ganglioside homologues were completely absent. This unusual ganglioside pattern suggests that the defect in GM3 (hematoside) sphingolipodystrophy is in ganglioside biosynthesis, in contrast to previously described sphingolipidoses, which are due to deficiencies of catabolic enzymes. (N Engl J Med 291:929–931, 1974)
Atypical antipsychotics and weightgain — a systematic review (2000)

All atypical drugs, with the exception of ziprasidone, have been associated with weight increases. Clozapine seems to have the highest risk of weight gain, followed by olanzapine and quetiapine. There is probably a lower risk with risperidone, sertindole and zotepine and a still lower risk with amisulpride. Ziprasidone appears not to be associated with weight gain. In the absence of more compelling data, these rankings must be considered approximate and preliminary. Longer, more robust trials are needed.
Immunohistochemical detection of the cyclin-dependent kinase inhibitor 2/multiple tumor suppressor gene 1 (CDKN2/MTS1) product p16INK4A in archival human solid tumors: correlation with retinoblastoma protein expression. (1995)

The retinoblastoma (RB) and cyclin-dependent kinase inhibitor 2/multiple tumor suppressor gene 1 (CDKN2/MTS1) tumor suppressor genes play important roles in the regulation of the cell cycle. The protein products of these two genes, pRB and p16INK4A ("p16"), respectively, inhibit progression from G1 to S phase. Moreover, p16 has been shown to exert its function through inhibition of CDK4-mediated phosphorylation of pRB. Both genes have been found to be mutated or deleted in a wide range of primary human tumors and tumor cell lines. However, the presence of CDKN2/MTS1 containing nonneoplastic elements in every tumor specimen may contribute to the apparent lower deletion detection rate in resected neoplasms compared to cell lines. We have developed an immunohistochemical assay that allows us to assess p16 expression in formalin-fixed, paraffin-embedded tissues. As controls, we used paraffin-embedded pellets of cell lines with well-defined p16 status (four positive and four negative lines), as well as routinely processed nude mouse xenografts of two p16-positive cell lines. p16-negative cells were characterized by the absence of nuclear staining, whereas cytoplasmic staining was variable. In neoplastic and normal tissues, the level of p16 generally appeared to be low. We tested 75 random human malignancies from 4 different anatomic sites for p16 expression and correlated the findings with the immunohistochemical presence or absence of pRB. Twenty % of tumors selectively lacked pRB, while 37% of neoplasms had undetectable p16. In 43% of all carcinomas, both pRB and p16 could be detected. Significant differences existed in the expression of both tumor suppressor genes between carcinomas from different sites. Breast cancers had the highest rate of p16 negativity (13 of 20). Our data show that: (a) immunohistochemistry may be a suitable modality to screen for RB and CDKN2/MTS1 abnormalities in paraffin-embedded tissues; (b) undetectable levels of p16 expression occur at a relatively high frequency; (c) p16 and pRB expression in common human malignancies is not mutually exclusive; (d) loss of function of both tumor suppressor genes appears to be a distinctly uncommon phenomenon; and (e) different types of carcinomas have variable rates of disturbance in the p16/pRB pathway.
Insulin Stimulates cAMP-response Element Binding Protein Activity in HepG2 and 3T3-L1 Cell Lines (1998)

Earlier studies from our laboratory demonstrated an insulin-mediated increase in cAMP-response element binding protein (CREB) phosphorylation. In this report, we show that insulin stimulates both CREB phosphorylation and transcriptional activation in HepG2 and 3T3-L1 cell lines, models of insulin-sensitive tissues. Insulin stimulated the phosphorylation of CREB at serine 133, the protein kinase A site, and mutation of serine 133 to alanine blocked the insulin effect. Many of the signaling pathways known to be activated by insulin have been implicated in CREB phosphorylation and activation. The ability of insulin to induce CREB phosphorylation and activity was efficiently blocked by PD98059, a potent inhibitor of mitogen-activated protein kinase kinase (MEK1), but not significantly by rapamycin or wortmannin. Likewise, expression of dominant negative forms of Ras or Raf-1 completely blocked insulin-stimulated CREB transcriptional activity. Finally, we demonstrate an essential role for CREB in insulin activation of fatty-acid synthase and fatty acid binding protein (FABP) indicating the potential physiologic relevance of insulin regulation of CREB. In summary, insulin regulates CREB transcriptional activity in insulin-sensitive tissues via the Raf --> MEK pathway and has an impact on physiologically relevant genes in these cells.
Catheter Tip Granuloma Associated with Sacral Region Intrathecal Drug Administration (2003)

Spinal cord compression from catheter tip granulomatous masses following intrathecal drug administration may produce devastating permanent neurologic deficits. Some authors have advocated intrathecal catheter placement below the conus medullaris to avoid the possibility of spinal cord involvement. Multiple cases of catheter tip granulomas in the thoracolumbar region have been reported. We present a unique case of a sacral region catheter tip inflammatory mass producing permanent neurologic deficits. A 71-year-old white male with a diagnosis of failed back surgery syndrome was referred to the senior author for evaluation. After more extensive conservative therapy, including spinal cord stimulation, failed to yield adequate pain relief, he was offered implantation of an intrathecal pump for opioid administration. Excellent pain relief was achieved in the postoperative period; however, three years after implantation, he presented with progressive saddle anesthesia and bowel/bladder incontinence. Magnetic resonance imaging demonstrated a space occupying lesion associated with the catheter tip. The patient underwent emergent second level complete sacral laminectomy with partial resection of an intradural extra-axial mass and removal of intrathecal catheter. At discharge, the patient had no restoration of neurologic function. Histologic examination of the mass confirmed a sterile inflammatory mass. It has been suggested that intrathecal catheters be placed below the conus medullaris to avoid the possibility of spinal cord involvement. We present an unusual case documenting devastating permanent neurologic deficits from a catheter tip granuloma in the sacral region.
Living-Related Liver Transplantation for Siblings with Progressive Familial Intrahepatic Cholestasis 2, with Novel Genetic Findings (2011)

Progressive familial intrahepatic cholestasis is a syndrome of severe cholestasis progressing to biliary cirrhosis and liver failure that develops in childhood. This report describes two siblings with PFIC-2 who underwent living-related liver transplantation from their genetically proven heterozygous parents. Both patients had normal gamma-glutamyl transpeptidase levels, but showed severe pruritus with sleep disturbance, cholestasis, jaundice and growth failure. Genetic testing of each patient revealed two missense mutations of the bile salt export pump, S901R and C1083Y, which have not previously been associated with PFIC-2. Usual medical treatment failed to improve their clinical symptoms, and the two siblings underwent living-related liver transplantation from their heterozygous parents. The transplants improved their clinical symptoms significantly, and the patients have since shown age-appropriate growth. Electron microscopic findings of the explanted liver of the younger sister revealed dense and amorphous bile, which is characteristic of PFIC-2. In the cases presented here, living-related liver transplantation from a heterozygous donor was associated with better quality of life and improvement of growth, and thus appears to be a feasible option for PFIC-2 patients. Mutation analysis is a useful tool to help decide the course of treatment of PFIC.
Analysis of lysozyme‐specific immune responses by synthetic peptides. I. Characterization of antibody and T cell‐mediated responses to the N‐terminal peptide of hen egg‐white lysozyme (1986)

The immunological reactivity against the N-terminal region of hen egg-white lysozyme (HEL) has been investigated by a synthetic peptide (PHEL) comprising residue 1-18 of HEL and by an analogue peptide (PREL) in which phenylalanine at position 3 is substituted by tyrosine. Both peptides are immunogenic in (C57BL/10 X DBA/2)F1 mice genetically responder to HEL. In C57BL/6 mice, genetically nonresponder to HEL, PREL induces anti-peptide antibodies that also bind to PHEL whereas PHEL is not immunogenic. Thus, a single amino acid substitution in a synthetic peptide converts a nonresponder mouse strain into a responder one. Anti-PHEL antibodies demonstrate a higher binding to HEL than anti-PREL antibodies, indicating that phenylalanine at position 3 is important for induction of anti-peptide antibodies able to recognize native HEL. At the T cell level the two peptides show very high bidirectional cross-reactivity between themselves and with HEL for interleukin 2 production, antigen-specific proliferation and delayed-type hypersensitivity response, whereas conservation of phenylalanine at position 3 is required for induction of suppressor cells cross-reactive with HEL. This indicates that the N-terminal region of HEL contains epitope(s) able to induce the same level of helper T cell activity as the native HEL molecule. However, helper T cells do not discriminate between PHEL and PREL whereas phenylalanine at position 3 is critical for HEL-specific suppressor T cell induction.
Toll-Like Receptors 4 and 5 Induce Distinct Types of Vasculitis (2009)

Large vessel vasculitides, such as Takayasu arteritis and giant cell arteritis, affect vital arteries and cause clinical complications by either luminal occlusion or vessel wall destruction. Inflammatory infiltrates, often with granulomatous arrangements, are distributed as a panarteritis throughout all of the artery's wall layers or cluster in the adventitia as a perivasculitis. Factors determining the architecture and compartmentalization of vasculitis are unknown. Human macrovessels are populated by indigenous dendritic cells (DCs) positioned in the adventitia. Herein, we report that these vascular DCs sense bacterial pathogens and regulate the patterning of the emerging arteritis. In human temporal artery-SCID chimeras, lipopolysaccharides stimulating Toll-like receptor (TLR)4 and flagellin stimulating TLR5 trigger vascular DCs and induce T-cell recruitment and activation. However, the architecture of the evolving inflammation is ligand-specific; TLR4 ligands cause transmural panarteritis and TLR5 ligands promote adventitial perivasculitis. Underlying mechanisms involve selective recruitment of functional T cell subsets. Specifically, TLR4-mediated DC stimulation markedly enhances production of the chemokine CCL20, biasing recruitment toward CCL20-responsive CCR6(+) T cells. In adoptive transfer experiments, CCR6(+) T cells produce an arteritis pattern with media-invasive T cells damaging vascular smooth muscle cells. Also, CCR6(+) T cells dominate the vasculitic infiltrates in patients with panarteritic giant cell arteritis. Thus, depending on the original danger signal, vascular DCs edit the emerging immune response by differentially recruiting specialized T effector cells and direct the disease process toward distinct types of vasculitis.
Longitudinal ambulatory measurements of gait abnormality in dystrophin-deficient dogs (2011)

The gait variables measured by the accelerometers were sensitive to early detect and follow the gait disorders and mirrored the heterogeneity of clinical presentations, giving sense to monitor gait in GRMD dogs during progression of the disease and pre-clinical therapeutic trials.
Quality of Life and Social Inclusion (2007)

The concepts of quality of life, anomie or marginalisation and social capital are introduced in the context of the impact of the post-modernising forces of globalisation, urbanisation, and mass migration on societal structures. Empirical relationships between the three concepts were explored using data derived from a study undertaken in south east Queensland, Australia in 2003. On the basis of descriptive statistics and a path analysis using LISREL procedures it was shown that although the majority of people did not feel marginalised and reported good quality of life, reduced quality of life was associated with low prestige occupations mediated by marginalisation or anomie. In addition social capital was found to improve quality of life both directly and by ameliorating marginalisation.
The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756) − a selective CXCR2 antagonist − in healthy adult subjects (2015)

ClinicalTrials.gov identifiers: NCT01209052 and NCT01209104.
Interaction between a membrane‐associated serine proteinase of U‐937 monocytes and peptides from the V3 loop of the human immunodeficiency virus type 1 (HIV‐1) gp120 envelope glycoprotein (1993)

A trypsin-like proteinase which is inhibited by recombinant gp120 and by synthetic peptides of various lengths spanning the conserved sequence of the V3 loop has been purified and partially characterized from a U-937 cell membrane extract. V3 loop peptides behave as competitive inhibitors of the enzyme, while gp120 exerts a tight-binding inhibition, reacting in stoichiometric amounts with the proteinase to provide significant inhibition. Though the properties of the U-937 membrane proteinase towards gp120 and synthetic peptides of the V3 loop resemble those of the Molt-4 T-cell tryptase TL2, these two proteinases differ by their physicochemical properties and their susceptibility to other inhibitors of serine proteinases. These results give support to the concept of a membrane-associated proteinase as a complementary or alternative receptor to the CD4, for allowing virus to enter host cells and thus spreading HIV infection.