Objective: To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition.
Methods: Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4-25 years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls.
Results: Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC.
Objective: Previous research suggests attention and white matter (WM) abnormalities in individuals with mucopolysaccharidosis type I (MPS I); this cross-sectional comparison is one of the first to examine the relationship of WM structural abnormalities as measured by corpus callosum (CC) volumes with attention scores to evaluate this relationship in a larger sample of patients with MPS I.
Methods: Volumetric MRI data and performance on a computerized measure of sustained attention were compared for 18 participants with the severe form of MPS I (MPS IH), 18 participants with the attenuated form of MPS I (MPS I), and 60 typically developing age-matched controls.
Results: The MPS I groups showed below-average mean attention scores ( < 0.
Antigen-specific CD4 T cell responses to (Mtb) infection are important for host defense against tuberculosis (TB). However, Mtb-specific IFN-γ-producing T cells do not distinguish active tuberculosis (ATB) patients from individuals with asymptomatic latent Mtb infection (LTBI). We reasoned that the immune phenotype of Mtb-specific IFN-γCD4 T cells could provide an indirect gauge of Mtb antigen load within individuals.
View Article and Find Full Text PDFNeutrophils are increasingly associated with tuberculosis (TB) disease. Neutrophil extracellular traps (NETs), which are released by neutrophils as a host antimicrobial defense mechanism, are also associated with tissue damage. However, a link between NET levels and TB disease has not been studied.
View Article and Find Full Text PDFObjectives: Precise characterization of cognitive outcomes and factors that contribute to cognitive variability will enable better understanding of disease progression and treatment effects in mucopolysaccharidosis type I (MPS I). We examined the effects on cognition of phenotype, genotype, age at evaluation and first treatment, and somatic disease burden.
Methods: Sixty patients with severe MPS IH (Hurler syndrome treated with hematopoietic cell transplant and 29 with attenuated MPS I treated with enzyme replacement therapy), were studied with IQ measures, medical history, genotypes.
Background: The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient's sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results.
View Article and Find Full Text PDFObjectives: Nosocomial pathogens such as Acinetobacter baumannii are a growing public health threat, due in part to their increasing resistance to antibiotics. Since some strains are resistant to all available antibiotics, novel therapies are urgently needed. Plasmablasts are short-lived B cells found in the blood that can be collected and harnessed to produce therapeutic antibodies.
View Article and Find Full Text PDFUnlabelled: The lysosomal enzyme α-L-iduronidase hydrolyzes terminal iduronic acid from heparan sulfate and dermatan sulfate, and is an essential step in GAG degradation. Mutations of its gene, IDUA, yield a spectrum of mucopolysaccharidosis (MPS) type I clinical disorders. The IDUA mutation, c.
View Article and Find Full Text PDFThe alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This problem is compounded by the absence of new antibiotics close to regulatory approval. Acinetobacter baumannii is a human pathogen that causes infections primarily in patients in intensive care units (ICUs) and is highly antibiotic resistant.
View Article and Find Full Text PDFAddiction to cocaine is associated with persistent changes in synaptic function. The cycling of actin between polymerized [F (for filamentous)] and depolymerized forms contributes to synaptic plasticity, and acute and withdrawal from repeated cocaine administration produced reversible and enduring elevations, respectively, in F-actin in the nucleus accumbens. Increased F-actin after 3 weeks withdrawal from repeated cocaine resulted from changes in the content or phosphorylation state of actin binding proteins (ABPs) that cosediment with F-actin.
View Article and Find Full Text PDFHomer proteins are integral to the assembly of proteins regulating glutamate signaling and synaptic plasticity. Constitutive Homer2 gene deletion [knock-out (KO)] and rescue with adeno-associated viral (AAV) transfection of Homer2b was used to demonstrate the importance of Homer proteins in neuroplasticity produced by repeated ethanol (EtOH) administration. Homer2 KO mice avoided drinking high concentrations of EtOH and did not develop place preference or locomotor sensitization after repeated EtOH administration.
View Article and Find Full Text PDFThe projection from the nucleus accumbens to the ventral pallidum regulates the reinstatement of cocaine seeking in rats extinguished from cocaine self-administration. This projection coexpresses GABA and enkephalin, posing a role for mu-opioid receptors in the ventral pallidum in mediating the reinstatement of cocaine seeking. Rats were extinguished from cocaine self-administration, and the reinstatement of active lever pressing by cocaine was blocked by intra-ventral pallidum administration of the mu receptor antagonist Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) (0.
View Article and Find Full Text PDFAlcohol Clin Exp Res
March 2005
Background: An increased level of extracellular glutamate is a key neurochemical feature associated with ethanol exposure and withdrawal.
Methods: In the current study, extracellular levels of glutamate and glutamate transport in the nucleus accumbens were assayed 24 hr after repeated ethanol exposure (1 g/kg ip daily for 7 days) with use of in vivo no-net-flux microdialysis and in vitro [(3)H]glutamate uptake, respectively.
Results: Microdialysis revealed higher extracellular glutamate concentrations in the nucleus accumbens of rats that were given ethanol.