gebhart/patrepeval huggingface dataset:
Deleterious Effects of High Dose Connexin 43 Mimetic Peptide Infusion After Cerebral Ischaemia in Near-Term Fetal Sheep (2012)

Hypoxic-ischaemic brain injury at birth is associated with 1-3/1000 cases of moderate to severe encephalopathy. Previously, we have shown that connexin 43 hemichannel blockade, with a specific mimetic peptide, reduced the occurrence of seizures, improved recovery of EEG power and sleep state cycling, and improved cell survival following global cerebral ischaemia. In the present study, we examined the dose response for intracerebroventricular mimetic peptide infusion (50 μmol/kg/h for 1 h, followed by 50 μmol/kg/24 h (low dose) or 50 μmol/kg/h for 25 h (high dose) or vehicle only (control group), starting 90 min after the end of ischaemia), following global cerebral ischaemia, induced by 30 min bilateral carotid artery occlusion, in near-term fetal sheep (128 ± 1 days gestation). Both peptide infusion groups were associated with a transient significant increase in EEG power between 2-12 h after ischaemia. The ischaemia-low dose group showed a significant recovery of EEG power from day five compared to the ischaemia-vehicle and -high dose groups. In contrast, the high dose infusion was associated with greater secondary increase in impedance (brain cell swelling), as well as a trend towards a greater increase in lactate concentration and mortality. These data suggest that higher doses of connexin mimetic peptide are not beneficial and may be associated with adverse outcomes, most likely attributable to uncoupling of connexin 43 gap junctions leading to dysfunction of the astrocytic syncytium.
The DNA-dependent Protein Kinase Is Inactivated by Autophosphorylation of the Catalytic Subunit (1996)

The DNA-dependent protein kinase (DNA-PK) requires for activity free ends or other discontinuities in the structure of double strand DNA. In vitro, DNA-PK phosphorylates several transcription factors and other DNA-binding proteins and is thought to function in DNA damage recognition or repair and/or transcription. Here we show that in vitro DNA-PK undergoes autophosphorylation of all three protein subunits (DNA-PKcs, Ku p70 and Ku p80) and that phosphorylation correlates with inactivation of the serine/threonine kinase activity of DNA-PK. Significantly, activity is restored by the addition of purified native DNA-PKcs but not Ku, suggesting that inactivation is due to autophosphorylation of DNA-PKcs. Our data also suggest that autophosphorylation results in dissociation of DNA-PKcs from the Ku-DNA complex. We suggest that autophosphorylation is an important mechanism for the regulation of DNA-PK activity.
Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism (2008)

Monoacyglycerol acyltransferases (MGATs) and diacylglycerol acyltransferases (DGATs) catalyze two consecutive steps of enzyme reactions in the synthesis of triacylglycerols (TAGs). The metabolic complexity of TAG synthesis is reflected by the presence of multiple isoforms of MGAT and DGAT enzymes that differ in catalytic properties, subcellular localization, tissue distribution, and physiological functions. MGAT and DGAT enzymes play fundamental roles in the metabolism of monoacylglycerol (MAG), diacylglycerol (DAG), and triacylglycerol (TAG) that are involved in many aspects of physiological functions, such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, signal transduction, satiety, and lactation. The recent progress in the phenotypic characterization of mice deficient in MGAT and DGAT enzymes and the development of chemical inhibitors have revealed important roles of these enzymes in the regulation of energy homeostasis and insulin sensitivity. Consequently, selective inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel treatment for obesity and its related metabolic complications.
In vivovisualization of macrophage infiltration and activity in inflammation using magnetic resonance imaging (2009)

Because macrophages play a key role on host defense, visualization of the migration of these cells is of high relevance for both diagnostic purposes and the evaluation of therapeutic interventions. The present article addresses the use of iron oxide and gadolinium-based particles for the noninvasive in vivo detection of macrophage infiltration into inflamed areas by magnetic resonance imaging (MRI). A general introduction on the functions and general characteristics of macrophages is followed by a discussion of some of the agents and acquisition schemes currently used to track the cells in vivo. Attention is then devoted to preclinical and clinical applications in the following disease areas: atherosclerosis and myocardial infarction, stroke, multiple sclerosis, rheumatoid arthritis, and kidney transplantation.
Microvascular perfusion upon exchange transfusion with stored red blood cells in normovolemic anemic conditions (2004)

Circulation of stored RBCs in a hemodiluted animal resulted in significantly malperfused and underoxygenated microvasculature that was not detectable at the systemic level.
HER-2, gp100, and MAGE-1 Are Expressed in Human Glioblastoma and Recognized by Cytotoxic T Cells (2004)

It has recently been demonstrated that malignant glioma cells express certain known tumor-associated antigens, such as HER-2, gp100, and MAGE-1. To further determine the possible utilization of these antigens for glioma immunotherapy and as surrogate markers for specific tumor antigen cytotoxicity, we characterized the presence of mRNA and protein expression in 43 primary glioblastoma multiforme (GBM) cell lines and 7 established human GBM cell lines. HER-2, gp100, and MAGE-1 mRNA expression was detected in 81.4%, 46.5%, and 39.5% of the GBM primary cell lines, respectively. Using immunoreactive staining analysis by flow cytometry, HER-2, gp100, and MAGE-1 protein expression was detected in 76%, 45%, and 38% of the GBM primary cell lines, respectively. HLA-A1-restricted epitope specific for MAGE-1 peptide (EADPTGHSY) CTL clone B07 and HLA-A2-restricted epitope specific for HER-2 peptide (KIFGSLAFL) CTL clone A05 and gp100 peptide (ITDQVPFSV) CTL clone CK3H6 were used in this study. The specificity of CTL clone was verified by HLA/peptide tetramer staining. Three CTL clones could efficiently recognize GBM tumor cells in an antigen-specific and MHC class I-restricted manner. IFN-gamma treatment can dramatically increase MHC class I expression of GBM tumor cells and significantly increase CTL recognition of tumor cells. Treatment with the DNA hypomethylating agent 5-aza-2'-deoxycytidine induced and up-regulated the mRNA expression of MAGE-1 and epitope presentation by autologous MHC. These data indicate that HER-2, gp100, and MAGE-1 could be used as tumor antigen targets for surrogate assays for antigen-specific CTLs or to develop antigen-specific active immunotherapy strategies for glioma patients.
Genes Essential for Amber Disease in Grass Grubs Are Located on the Large Plasmid Found in Serratia entomophila and Serratia proteamaculans (1995)

The bacteria Serratia entomophila and S. proteamaculans cause amber disease in the grass grub, Costelytra zealandica (Coleoptera: Scarabaeidae), an important pasture pest in New Zealand. Disease symptoms include rapid cessation of feeding and amber coloration of larvae. A 105-kb plasmid (designated pADAP) has consistently been found only in pathogenic isolates of both species. Investigations into the involvement of pADAP in amber disease have been hindered by the lack of both a selectable marker on the plasmid and a reliable transposon delivery system. Kanamycin-resistant transposon insertions into three cloned HindIII fragments (9.5, 9.6, and 10.6 kb) were isolated and introduced into pADAP by shuttle mutagenesis. Inserts into the 9.5-and 9.6-kb HindIII fragments on pADAP did not alter disease-causing ability. When plasmids with inserts into the 9.6-kb region were conjugated into plasmid-minus, nonpathogenic isolates of S. entomophila and S. proteamaculans, all of them became pathogenic. Transposon insertions into two regions of the 10.6-kb HindIII fragment continued to cause cessation of feeding but failed to produce amber coloration. Further analysis of a mutant from each amber-minus region (pADK-10 and pADK-13) demonstrated that the antifeeding effect was produced only at dosages higher than that of the wild-type strain. Complementation with the wild-type HindIII fragment restored full-blown disease properties for pADK-13, but not for pADK-10.
Research Issues and Ideas in Statistical Process Control (1999)

An overview is given of current research on control charting methods for process monitoring and improvement. The discussion includes a historical perspective along with ideas for future research. Research topics include, for example, variable sample size and sampling interval methods, economic designs, attribute data methods, charts based on autocorrelated observations, multivariate methods, and nonparametric methods. Recommendations and references are provided to those interested in pursuing research ideas in statistical process control (SPC). Some issues regarding the relevance of SPC research are also discussed.
The myelodysplastic syndromes: Diagnosis, molecular biology and risk assessment (2005)

Myelodysplastic syndromes (MDS) are heterogeneous group of neoplastic clonal stem cell diseases characterized by dysplastic morphological features and clinical bone marrow failure. The FAB (French-American-British) system served as the gold standard for MDS classification for more than two decades. The WHO classification, built on the backbone of FAB classification, is an attempt to further improve the prognostic value of MDS classification as well as establish its clinical utility as a tool to select different treatments. In this article we review the epidemiology, pathogenesis, molecular biology, diagnosis and classification of MDS. We highlight the major differences between the FAB classification and the WHO MDS classification. We discuss in more detail the experience of using the new WHO classification since its publication and review the studies that tried to validate the prognostic value of the new classification or apply it to predict clinical responses to various treatments.
Expression of varicella-zoster virus in blood mononuclear cells of patients with postherpetic neuralgia. (1988)

Postherpetic neuralgia (PHN), the most frequent complication of varicella-zoster virus (VZV) reactivation, is characterized by pain that persists for greater than 1 mo and often for years after zoster rash. To examine whether PHN might be related to reactivation of VZV, blood mononuclear cells of patients with PHN were tested for the presence of VZV DNA and proteins. VZV DNA was detected in the mononuclear cells of one PHN patient. VZV-specific proteins were detected in mononuclear cells of two acute-varicella patients, one acute zoster patient, and six elderly patients with PHN, but these VZV-specific proteins were not detected in three elderly zoster patients without PHN. Furthermore, pulse-chase experiments revealed further processing or degradation of VZV-specific proteins in the mononuclear cells. These findings strongly suggest that persistence, reactivation, and expression of VZV may result in PHN.
Care of persons with AIDS in the nursing home. (1998)

AIDS is becoming a chronic illness for some patients whose significant accumulated functional impairments may limit community-based care. Nursing homes can provide an appropriate level of care, although reported experience caring for persons with AIDS in this setting is limited.A retrospective case-series review was conducted in a 242-bed community teaching nursing home to describe the initial 26-month experience in providing care for patients with AIDS requiring nursing home admission.A total of 42 admissions by 32 patients with AIDS (mean age = 33.5 years, 81% male) involved a shorter length of stay (mean 63.1 days) and higher numbers of medications (mean = 11.2), facility charges (mean $11,971/admission, $189/day), and greater clinical management complexity than usual nursing home patients. Thirteen patients were discharged, seven for rehospitalization and six into community settings, although ultimately 29 of the 32 patients died in the facility.AIDS care in the nursing home presents significant, distinct challenges in complex management and terminal care prioritization.
Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD). (1997)

A positive influence of magnesium in the prevention and treatment of hyperactivity in children is more and more frequently raised in the literature. The aim of our work was to estimate magnesium contents in children with attention deficit hyperactivity disorder, (ADHD). The investigations comprised 116 children (94 boys and 20 girls), aged 9-12 years, with recognized ADHD. In 68 out of 116 patients examined ADHD occurred with other coexisting disorders specific to the developmental age and in the remaining 48 patients it occurred together with disruptive behaviour. Magnesium levels have been determined in blood serum, red blood cells and in hair with the aid of atomic absorption spectroscopy. Magnesium deficiency was found in 95 per cent of those examined, most frequently in hair (77.6 per cent), in red blood cells (58.6 per cent) and in blood serum (33.6 per cent) of children with ADHD. The conclusion from the investigations is that magnesium deficiency in children with ADHD occurs more frequently than in healthy children. Analysis of the material indicated the correlation between levels of magnesium and the quotient of development to freedom from distractibility.
The Effect of a High‐Fat Meal on the Oral Bioavailability of the Immunosuppressant Sirolimus (Rapamycin) (1999)

The bioavailability of an oral nonaqueous solution of sirolimus was compared under fasting conditions and after a high-fat meal in a randomized, two-way crossover pharmacokinetic study. Healthy volunteers were administered a 15 mg single dose of sirolimus on two occasions, once while fasting and once after consumption of a high-fat breakfast. Whole blood concentrations of sirolimus were assayed by using a validated method with high-performance liquid chromatography/tandem mass spectrometric detection. Sirolimus was absorbed more slowly when administered after a high-fat meal than when administered after fasting, as shown by statistically significant reductions in peak concentration (Cmax) and the ratio of Cmax to the area under the curve (AUC), and lengthening of the time to peak concentration. The oral availability of sirolimus was increased to a modest extent (35%) and in a uniform manner when administered with a high-fat meal; the geometric mean ratio of the fed/fasting AUC values was 1.35, with a 90% confidence interval of 1.26 to 1.46. Food had no effect on the terminal half-life of sirolimus (mean values of 67 to 68 hours). The 35% increase in AUC obtained after a high-fat meal appears small relative to the intersubject and intrasubject variabilities observed in clinical trials. However, to minimize unnecessary fluctuations in trough whole blood sirolimus concentrations, it is advisable that sirolimus be administered consistently in individual patients, either with or without meals.
Glycophorin as a Receptor for Sendai Virus (1996)

Glycophorin A was reconstituted into large unilamellar vesicles of egg phosphatidylcholine by detergent dialysis. The observed overall rate of Sendai virus fusion increased approximately 4-fold between 0 and 0.006 mol % glycophorin, roughly proportional to the glycophorin content. However, no further increase in rate was observed at 0.02 mol % glycophorin. Treatment of reassembled glycophorin-liposomes with neuraminidase resulted in a significant decrease in the percent of viral fusion, confirming that the presence of sialic acid residues on glycophorin is essential for its role as a receptor. The sialic acid-containing glycolipid, the ganglioside GD1a, was also incorporated into phosphatidylcholine liposomes, either in addition to or in place of glycophorin A. Comparing, on the basis of sialic acid content, liposomes containing either glycophorin or GD1a, comparable rates and extents of fusion were found. However, on a molar basis glycophorin is much more effective. It was found that the addition of GD1a to glycophorin-containing liposomes only slightly increased the rate of fusion. This was largely due to an increase in the percent of virions capable of fusing.
Delineation of two defects responsible for T-cell hyporesponsiveness to concanavalin A in MRL congenic mice. (1986)

MRL-lpr mice and their congenic counterparts MRL-+ spontaneously develop an autoimmune disease that resembles systemic lupus erythematosus in humans. The two strains, although congenic, differ by a considerable number of disease parameters, reflecting the expression of the lpr autosomal recessive gene. One paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigated a possible lpr gene-encoded macrophage defect in these mice. It was found, however, that both the MRL-+ and MRL-lpr mice failed to divide in response to Con A, the lack of division correlating with an inability to secrete the growth promoter interleukin-2. In MRL-+ mice and young MRL-lpr mice this non-responsiveness was corrected by the addition of normal CBA PEC. The defect could not be explained by a failure of MRL-+ or MRL-lpr peritoneal exudate cells to quantitatively or qualitatively provide a source of interleukin-1 to Con A-activated T cells or by the possibility that the peritoneal exudate cells were blocked in their function by the presence of sera-derived autoantibodies and/or immune complexes on their membranes. We postulate that the inability of T cells to proliferate in MRL congenic mice can be explained by two defects: the failure of antigen-presenting cells in MRL-+ and MRL-lpr to provide the necessary signals to immunocompetent T cells, this defect not being associated with the lpr gene, and the lpr gene controlled outgrowth of a unique T-cell population that cannot respond in our assay system.
p56Lck and p59Fyn regulate CD28 binding to phosphatidylinositol 3-kinase, growth factor receptor-bound protein GRB-2, and T cell-specific protein-tyrosine kinase ITK: implications for T-cell costimulation. (1995)

T-cell activation requires cooperative signals generated by the T-cell antigen receptor zeta-chain complex (TCR zeta-CD3) and the costimulatory antigen CD28. CD28 interacts with three intracellular proteins-phosphatidylinositol 3-kinase (PI 3-kinase), T cell-specific protein-tyrosine kinase ITK (formerly TSK or EMT), and the complex between growth factor receptor-bound protein 2 and son of sevenless guanine nucleotide exchange protein (GRB-2-SOS). PI 3-kinase and GRB-2 bind to the CD28 phosphotyrosine-based Tyr-Met-Asn-Met motif by means of intrinsic Src-homology 2 (SH2) domains. The requirement for tyrosine phosphorylation of the Tyr-Met-Asn-Met motif for SH2 domain binding implicates an intervening protein-tyrosine kinase in the recruitment of PI 3-kinase and GRB-2 by CD28. Candidate kinases include p56Lck, p59Fyn, zeta-chain-associated 70-kDa protein (ZAP-70), and ITK. In this study, we demonstrate in coexpression studies that p56Lck and p59Fyn phosphorylate CD28 primarily at Tyr-191 of the Tyr-Met-Asn-Met motif, inducing a 3- to 8-fold increase in p85 (subunit of PI 3-kinase) and GRB-2 SH2 binding to CD28. Phosphatase digestion of CD28 eliminated binding. In contrast to Src kinases, ZAP-70 and ITK failed to induce these events. Further, ITK binding to CD28 was dependent on the presence of p56Lck and is thus likely to act downstream of p56Lck/p59Fyn in a signaling cascade. p56Lck is therefore likely to be a central switch in T-cell activation, with the dual function of regulating CD28-mediated costimulation as well as TCR-CD3-CD4 signaling.
EXTRACTION OF CORONARY ARTERIAL TREE USING CINE X-RAY ANGIOGRAMS (2005)

An efficient and robust method for identification of coronary arteries and evaluation of the severity of the stenosis on the routine X-ray angiograms is proposed. It is a challenging process to accurately identify coronary artery due to poor signal-to-noise ratio, vessel overlap, and superimposition with various anatomical structures such as ribs, spine, or heart chambers. The proposed method consists of two major stages: (a) signal-based image segmentation and (b) vessel feature extraction. The 3D Fourier and 3D Wavelet transforms are first employed to reduce the background and noisy structures in the images. Afterwards, a set of matched filters was applied to enhance the coronary arteries in the images. At the end, clustering analysis, histogram technique, and size filtering were utilized to obtain a binary image that consists of the final segmented coronary arterial tree. To extract vessel features in terms of vessel centerline and diameter, a gradient vector-flow based snake algorithm is applied to determine the medial axis of a vessel followed by the calculations of vessel boundaries and width associated with the detected medial axis.
Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice (2005)

Here we report that a new nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse line harboring a complete null mutation of the common cytokine receptor gamma chain (NOD/SCID/interleukin 2 receptor [IL2r] gamma(null)) efficiently supports development of functional human hemato-lymphopoiesis. Purified human (h) CD34(+) or hCD34(+)hCD38(-) cord blood (CB) cells were transplanted into NOD/SCID/IL2rgamma(null) newborns via a facial vein. In all recipients injected with 10(5) hCD34(+) or 2 x 10(4) hCD34(+)hCD38(-) CB cells, human hematopoietic cells were reconstituted at approximately 70% of chimerisms. A high percentage of the human hematopoietic cell chimerism persisted for more than 24 weeks after transplantation, and hCD34(+) bone marrow grafts of primary recipients could reconstitute hematopoiesis in secondary NOD/SCID/IL2rgamma(null) recipients, suggesting that this system can support self-renewal of human hematopoietic stem cells. hCD34(+)hCD38(-) CB cells differentiated into mature blood cells, including myelomonocytes, dendritic cells, erythrocytes, platelets, and lymphocytes. Differentiation into each lineage occurred via developmental intermediates such as common lymphoid progenitors and common myeloid progenitors, recapitulating the steady-state human hematopoiesis. B cells underwent normal class switching, and produced antigen-specific immunoglobulins (Igs). T cells displayed the human leukocyte antigen (HLA)-dependent cytotoxic function. Furthermore, human IgA-secreting B cells were found in the intestinal mucosa, suggesting reconstitution of human mucosal immunity. Thus, the NOD/SCID/IL2rgamma(null) newborn system might be an important experimental model to study the human hemato-lymphoid system.
Accuracy in electronic speckle photography (1997)

Electronic speckle photography is an accurate, easy-to-use, video-based technique for the analysis of two- and three-dimensional deformation fields and in-plane strain fields, based on numerical cross correlation. Through the use of statistical optics, simulated speckle patterns, and experiments the accuracy in electronic speckle photography was found to depend on correlation, speckle size, window size, and correlation filter. The estimated correlation was found to be the combined effect of three mutually competing factors because of classical speckle correlation, subimage overlap, and displacement gradients. In many applications white-light speckle patterns provide a more accurate estimate of the displacement field than do laser speckle patterns.