Lesion-Specific and Vessel-Related Determinants of Fractional Flow Reserve Beyond Coronary Artery Stenosis

Objectives

The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR.

HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments

OBJECTIVE—To determine the predictive value of shared epitope alleles for response to treatment in patients with rheumatoid arthritis.
METHODS—Patients from our previously published triple DMARD study were tested for the presence of shared epitope alleles (DRB1 *0401,0404/0408, 0405,0101, 1001,and 1402). Patients who were shared epitope positive were then compared with those who were negative to see if there was a differential effect on therapeutic response.
RESULTS—Shared epitope positive patients were much more likely to achieve a 50% response if treated with methotrexate-sulphasalazine-hydroxychloroquine compared with methotrexate alone (94% responders versus 32%, p<0.0001). In contrast shared epitope negative patients did equally well regardless of treatment (88% responders for methotrexate-sulphasalazine-hydroxychloroquine versus 83% for methotrexate). Additionally, a trend toward an inverse relation of the gene dose was seen for response to methotrexate treatment (p=0.05).
CONCLUSIONS—These data suggest that determining shared epitope status may provide clinical information useful in selecting among treatment options.

Keywords: DRB1; rheumatoid arthritis; combination treatment; shared epitope     

Analysis of mutational status, SNP rs16754, and expression levels of Wilms tumor 1 (WT1) gene in acute promyelocytic leukemia

Overexpression, polymorphisms, and mutations of the WT1 gene have been reported in several human tumors including acute myeloid leukemia (AML) and variably correlated with prognosis. Acute promyelocytic leukemia (APL) represents the AML subset disclosing higher WT1 expression levels; however, no WT1 studies specifically focused on APL have been conducted. We screened for the presence of mutations, SNP rs16754, and expression levels of WT1 gene in 103 adult patients with newly diagnosed APL. Fms-like tyrosine kinase (FLT3) mutations were analyzed as well. WT1 mutations were identified in four (4?%) patients. At least one copy of the minor SNP rs16754 allele (WT1 ^AG or WT1 ^GG) was detected in 30 (29?%) patients. Six patients (6?%) were homozygous for the minor allele (WT1 ^GG ) and this genotype was associated with higher WT1 mRNA copies (p?=?0.018). FLT3 mutations were found in 37?% of patients and correlated with high WT1 mRNA expression (p?=?0.004). Patients heterozygous or homozygous for the minor allele and patients homozygous for major (WT1 ^AA) allele did not differ in terms of presenting features. In adult APL, WT1 gene mutational and polymorphic profile shows similarities with pediatric AML rather than with adult AML.     

The major histocompatibility complex, MnLA, of pigtailed Macaques: Definition of fifteen specificities

The major histocompatibility complex (MHC) of pigtailed macaques (Macaca nemestrina, Mn) is defined and designated as MnLA. Twenty-nine alloantisera were generated by fullsib alloimmunization and tested against a panel of 220 unrelated animals. The reactivities of different alloantisera were analyzed statistically in pairwise comparisons. Using 2 × 2 contingency tables, we calculated х² independence, х² allelism, and correlation coefficient values. Initially, specificities were defined by significant associations of certain sera, but some sera defined specificities individually. In all, 15 specificities were defined, and by family studies and negative correlation coefficients, a two-locus model was evident. Genetic analyses, together with statistical applications, revealed that the behavior of these specificities is consistent with the nature of MHC in other primate species, including man.     

A method for single-cell sorting and expansion of genetically modified human embryonic stem cells

Genetic modification of human embryonic stem (hES) cells is essential for studies of gene function and differentiation. The expression of transgenes may direct tissue-specific differentiation and aid in the identification of various differentiated cell types. Stable genomic integration of transgenes is optimal because hES cell differentiation can span several days to weeks and include numerous cell divisions, and establishing homogeneous modified cell lines will facilitate research studies. Herein we provide a method for producing and expanding hES cell lines from single cells that have been isolated by fluorescence-activated cell sorting (FACS) following genetic modification by lentivirus vectors. Using this method, we have established enhanced green fluorescent protein (eGFP)-expressing hES cell lines that are pluripotent, contain a diploid chromosomal content, and stably express eGFP following more than 2 months of routine culture and in vivo differentiation.     

Feasibility of a multiplex flow cytometric bead immunoassay for detection of anti-epoetin alfa antibodies

Immunogenicity profiles of recombinant therapeutic proteins are important to understand because antibodies raised against these molecules may have important clinical sequelae. The purpose of the present study was to demonstrate that a flow cytometric bead array could be used to detect clinically relevant antibodies with specificity to such therapeutics. We chose to evaluate well-characterized specimens from persons treated with epoetin alfa that developed antibody-mediated pure red blood cell aplasia as a means to demonstrate the utility of this platform. Our data show that this assay is capable of detecting anti-epoetin alfa antibodies with a relative antibody concentration of 50 ng/ml, where 25 of 25 sera spiked with antibodies at this concentration scored positive. Moreover, the assay was designed to include positive and negative control beads for each specimen that is processed to ensure the specificity of the signal when detected. Measurement of interassay precision supports quantitative estimates of relative antibody concentrations in the range of 313 to 5,000 ng/ml, where the percent coefficient of variation did not exceed 20%. With respect to clinical specimens, antibodies with specificity for epoetin alfa could be easily detected in a set of specimens from persons with pure red blood cell aplasia that had prior exposure to the EPREX brand of recombinant epoetin alfa. Further development and validation of this approach may facilitate successful widespread application of the method for detection of anti-epoetin alfa antibodies, as well as antibodies directed against other recombinant therapeutic proteins.     

Antagonistic Actinomycetes Mediated Resistance in <Emphasis Type="Italic">Solanum lycopersicon</Emphasis> Mill. Against <Emphasis Type="Italic">Rhizoctonia solani</Emphasis> Kühn

Actinomycetes are a major group of beneficial microbes, which can be explored as spanking alternative to chemical fungicides for providing defense against phytopathogens. Rhizoctonia solani is a major havoc causing severe loss to many crops. Biological measures for fungal disease management are desired over the available chemical/synthetic fungicides owing to their safety towards non-target organisms. In the present study, 34 actinomycetes were isolated from vermicompost. Out of them, twelve revealed antifungal activity related to Indole acetic acid (IAA) production, siderophores and plant growth promotion. Under greenhouse and field conditions, these potent strains remarkably enhanced yield attributes and disease diminution as compared to untreated control. A significant disease reduction of 47–63 % against R. solani was observed in tomato plants pretreated with actinomycetes. Furthermore, induction in defense related enzymes such as peroxidase, polyphenol oxidase, phenylalanine ammonia lyase, accumulation of phenolics and flavonoids were also observed in actinomycetes treated plants. Morphological and molecular characterization analysis identified these potent isolates as Streptomyces sp. NBM3, Streptomyces sp. NBM2, Streptomyces sp. NBM1, Streptomyces sp. NBM12 and Streptomyces sp. NBM8. The present findings suggest that these microbes can be utilized for significant enhancement of plant growth and augmentation of defense related enzymes in order to cope up with R. solani induced stress, thereby contributing to crop health.     

Evaluation of Biocompatibility and Osteogenic Potential of Tricalcium Silicate–based Cements Using Human Bone Marrow–derived Mesenchymal Stem Cells

Introduction

The success of endodontic regeneration lies in the appropriate combination of stem cells and bioactive materials. Several novel dental materials are available on the market in this regard. Hence, the current study aimed to evaluate the proliferation, differentiation, and osteogenic potential of human bone marrow–derived mesenchymal stem cells (hBMSCs) onto biomaterials like ProRoot MTA (MTA; Dentsply Tulsa Dental, Tulsa, OK), Biodentine (BD; Septodont, Saint Maur de Fosses, France), and EndoSequence Root Repair Material (ERRM; Brasseler USA, Savannah, GA).

Photocatalytic activity of Ni0.5Zn0.5Fe2O4@polyaniline decorated BiOCl for azo dye degradation under visible light – integrated role and degradation kinetics interpretation

Herein, we demonstrated the excellent improvement in photocatalytic degradation performance of BiOCl upon facile heterogeneous decoration with an integrated Ni_0.5Zn_0.5Fe₂O₄@polyaniline nanocomposite for an organic pollutant, methyl orange dye (MO), under visible light irradiation. The physico-chemical nature of the heterogeneous nanocomposite was characterized by XRD, FTIR, HRTEM-EDX and XPS analyses. The tuning of the band gap and optical sensitivity of BiOCl using Ni_0.5Zn_0.5Fe₂O₄@polyaniline were measured by DRS, PL and EIS techniques. To validate the transformation of the BiOCl photocatalyst to a visible light active photocatalyst due to the incorporation of Ni_0.5Zn_0.5Fe₂O₄@polyaniline and to gain insight into the origin of the synergistic effect for dye degradation by the heterostructured nanocomposite, we explored the effects of process parameters such as catalyst dosage, initial dye concentration, pH and the presence of inorganic anions on the extent of photo degradation. To get more details about reaction kinetics, a kinetic model using non-liner regression analysis was developed and the validity of the model was tested by comparing the experimental values with the calculated data. Based on the intermediate product formation, identified by GC-MS, a probable degradation pathway and a mechanism based on the electrochemical behaviour of the developed catalyst and trapping experiments were also proposed.

The photocatalytic activity of BiOCl is tuned through heterogeneous decoration with an integrated Ni_0.5Zn_0.5Fe₂O₄@polyaniline. The outstanding degradation capacity, effects of parameters on degradation kinetics and a kinetic model using regression analysis is reported.