inosinic-acid and Graft-vs-Host-Disease

Mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), inhibits inosine monophosphate dehydrogenase (IMPDH) activity. IMPDH is the rate-limiting enzyme involved in de novo synthesis of guanosine nucleotides and catalyzes the oxidation of inosine 5'-monophosphate to xanthosine 5'-monophosphate (XMP). We developed a highly sensitive liquid chromatography-mass spectrometry method to quantitate XMP concentrations in peripheral blood mononuclear cells (PMNCs) isolated from the recipient pretransplant and used this method to determine IMPDH activity in 86 nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) patients. The incubation procedure and analytical method yielded acceptable within-sample and within-individual variability. Considerable between-individual variability was observed (12.2-fold). Low recipient pretransplant IMPDH activity was associated with increased day +28 donor T cell chimerism, more acute graft-versus-host disease (GVHD), lower neutrophil nadirs, and more cytomegalovirus reactivation but not with chronic GVHD, relapse, nonrelapse mortality, or overall mortality. We conclude that quantitation of the recipient's pretransplant IMPDH activity in PMNC lysate could provide a useful biomarker to evaluate a recipient's sensitivity to MMF. Further trials should be conducted to confirm our findings and to optimize postgrafting immunosuppression in nonmyeloablative HCT recipients.

Topics: Acute Disease; Adult; Aged; Biomarkers; Female; Graft Survival; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Inosine Monophosphate; Leukocytes, Mononuclear; Male; Middle Aged; Mycophenolic Acid; Prognosis; Prospective Studies; Recurrence; Ribonucleotides; Survival Analysis; Transplantation Chimera; Transplantation, Homologous; Xanthine

Desistance scholars primarily focus on changing social roles, cognitive transformations, and shifting identities to understand the cessation of serious crime and illicit drug use in adulthood. In the current study, we move the spotlight away from adulthood and toward adolescence, the developmental stage when the prevalence of offending and substance use peak and desistance from most of these behaviors begins. Our primary hypothesis is that changes in perceived psychic rewards surrounding initial forays into marijuana use strongly predict adolescents' decisions to cease or persist that behavior. In addition, based on social learning expectations, we hypothesize that peer perceptions and behaviors provide mechanisms for perceptual change.. We find that changes in marijuana's perceived psychic rewards surrounding initiation differentiated experimenters from persisters. Experimenters had significantly lower updated perceptions of marijuana as a fun behavior compared to persisters and these perceptions dropped after the initiation wave. In contrast, persisters updated their perceptions in upward directions and maintained more positive perceptions over time. Inconsistent with social learning expectations, initiators' updated perceptions of marijuana as a fun activity were not explained by peer-reported behaviors or attitudes.

Topics: Adolescent; Adult; Age Factors; Aged; Amino Acid Substitution; Anemia, Aplastic; Athletes; Athletic Performance; Bone Marrow Transplantation; Carcinoma, Non-Small-Cell Lung; Catalytic Domain; Cell Count; Child; Child, Preschool; Escherichia coli; Female; Gene Expression; Graft Survival; Graft vs Host Disease; Histocompatibility Testing; Humans; Hydrogen Bonding; Immunosuppression Therapy; Inosine Monophosphate; Integrin alphaVbeta3; Kinetics; Knee Joint; Lung Neoplasms; Lymphatic Metastasis; Male; Mediastinal Neoplasms; Middle Aged; Molecular Dynamics Simulation; Muscle, Skeletal; Mutation; Organotechnetium Compounds; Pentosyltransferases; Peptides, Cyclic; Phenylalanine; Plasmodium falciparum; Protein Interaction Domains and Motifs; Protein Structure, Secondary; Protozoan Proteins; Radiopharmaceuticals; Recombinant Proteins; Running; Sensitivity and Specificity; Serine; Siblings; Single Photon Emission Computed Tomography Computed Tomography; Soccer; Structure-Activity Relationship; Substrate Specificity; Thermodynamics; Threonine; Time Factors; Torque; Treatment Outcome; Tryptophan; Tyrosine; Young Adult