ABSTRACT
OBJECTIVE: Vitamin D supplementation may be required for certain subgroups in the United States in whom status and intake are inadequate, but the impact of various doses, and whether calcium administration jointly or independently influences vitamin D metabolite levels, is unclear. METHODS: In a pilot chemoprevention trial of biomarkers of risk for colorectal adenoma, we measured the impact of vitamin D supplementation and/or calcium supplementation on plasma vitamin D metabolite concentrations. Ninety-two adult men and women living in the southeastern United States were randomized to 800 IU vitamin D(3), 2000 mg elemental calcium, both, or placebo daily for 6 months. We examined vitamin D status at baseline and postintervention and compared the change in plasma 25-hydroxyvitamin D (25(OH)D) and 1,25(OH)(2)D levels by intervention group using general linear models. RESULTS: Eighty-two percent of the study population had insufficient plasma 25(OH)D concentrations (<75 nmol/L) at baseline, with the lowest levels observed among African American participants. Vitamin D supplements, with or without calcium supplementation, raised plasma 25(OH)D concentrations, on average, by 25 to 26 nmol/L. Half of the study participants were classified as having sufficient 25(OH)D status after 6 months of 800 IU of vitamin D(3) daily. Calcium alone did not influence 25(OH)D concentrations. CONCLUSION: In this southeastern U.S. population, half of the study participants receiving 800 IU vitamin D(3) daily had blood 25(OH)D concentrations of Subject(s)
Calcium/administration & dosage
, Cholecalciferol/administration & dosage
, Dietary Supplements
, Vitamin D/analogs & derivatives
, Aged
, Alleles
, Analysis of Variance
, Chi-Square Distribution
, Double-Blind Method
, Female
, Genotype
, Georgia
, Humans
, Male
, Medication Adherence
, Middle Aged
, Pilot Projects
, Polymorphism, Single Nucleotide
, Receptors, Calcitriol/genetics
, Surveys and Questionnaires
, Treatment Outcome
, Vitamin D/blood
ABSTRACT
Dendritic cell (DC) immunotherapy is being actively studied in multiple myeloma (MM). We aimed to use positron emission tomography or single positron emission tomography to determine the in vivo distribution of monocyte-derived nonmatured DC or matured DC (mDC) administered to patients with MM. Eligible patients had stable or slowly progressive MM and elevated serum MUC-1 or MUC-1 expression on marrow plasma cells. DCs were derived from granulocyte-macrophage colony-stimulating factor+ interleukin-13 stimulated autologous monocytes, pulsed with mannan-MUC1 fusion protein, and matured by FMKp and interferon-gamma. Before injection, DCs were labeled with either 18fluorine-fluorodeoxyglucose, 111indium-oxine or 64copper-pyruvaldehyde-bis-N-4-methylthiosemicarbazone. Labeled DCs were given either as a single intravenous dose or by concurrent subcutaneous (SC), intradermal (ID), and intranodal routes. 18Fluorine-fluorodeoxyglucose tracking was unsuccessful owing to high radiolabel efflux. 64Copper-pyruvaldehyde-bis-N-4-methylthiosemicarbazone-labeled mDC (n=2 patients) demonstrated tracking to regional nodes but quantitation was also limited owing to cellular efflux. 111Indium-oxine, however, gave reproducible tracking of both nmDc and mDC (n=6) to regional lymph node after either SC or ID administration, with mDC revealing superior migration to regional lymph node. SC and ID routes produced similar levels of DC migration.
Subject(s)
Cell Movement/immunology , Dendritic Cells/transplantation , Multiple Myeloma/therapy , Aged , Antibodies/blood , Antibodies/immunology , Antigens, Bacterial/pharmacology , Antigens, CD/analysis , Cytokines/pharmacology , Dendritic Cells/drug effects , Dendritic Cells/pathology , Female , Fluorodeoxyglucose F18/chemistry , Humans , Interferon-gamma/metabolism , Klebsiella pneumoniae/immunology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Liver/metabolism , Liver/pathology , Lung/metabolism , Lung/pathology , Lymph Nodes/pathology , Male , Middle Aged , Mucin-1/blood , Mucin-1/immunology , Multiple Myeloma/metabolism , Multiple Myeloma/pathology , Organometallic Compounds/chemistry , Oxyquinoline/analogs & derivatives , Oxyquinoline/chemistry , Radiopharmaceuticals/chemistry , Spleen/pathology , Thiosemicarbazones/chemistry , Tomography, Emission-Computed/methodsABSTRACT
A genetic susceptibility to depression in PD, acting via the serotonergic system, has been suggested. We examined the influence of allelic variation (L/S) in a functional polymorphism in the serotonin transporter (5-HTTLPR) gene upon mood in 108 PD patients and 82 controls. Using a logistic regression model we found no evidence for an association between 5-HTTLPR genotypes, or the presence of the S allele, and depression.
Subject(s)
Depression/genetics , Parkinson Disease/genetics , Polymorphism, Genetic , Serotonin Plasma Membrane Transport Proteins/genetics , Aged , Alleles , Depression/epidemiology , Female , Genetic Predisposition to Disease/epidemiology , Genetic Variation , Humans , Logistic Models , Male , Middle Aged , Parkinson Disease/epidemiology , Promoter Regions, Genetic/genetics , Risk FactorsABSTRACT
There is increasing evidence that genetic variants of mitochondrial DNA have an important role in the cause of idiopathic Parkinson's disease. We determined the mitochondrial DNA haplogroup of 455 Parkinson's disease cases, 185 Alzheimer's disease cases, and 447 healthy English control subjects. The UKJT haplogroup cluster was associated with a 22% reduction in population-attributable risk for Parkinson's disease. There was no association between individual haplogroups or the UKJT cluster and Alzheimer's disease, confirming that the association with Parkinson's disease was disease specific and not a general effect seen in all neurodegenerative diseases.
