Fodrin and band 4.1 in a plasma membrane-associated fraction of human neutrophils

Erythrocytes possess a well-characterized submembranous filamentous network which interacts with transmembrane glycoproteins and is composed primarily of spectrin, ankyrin, band 4.1, and short actin filaments. An analogous structure was recently described in platelets. Human polymorphonuclear leukocytes (PMNs) were examined for the presence and plasma membrane association of similar proteins. Isolated PMNs, free of contamination with erythrocytes or platelets, were disrupted by nitrogen cavitation and separated into subcellular organelles on a discontinuous Percoll gradient. Detergent lysates of plasma membrane vesicles, but not azurophilic or specific granules, contained insoluble actin filaments and associated proteins. Immunoblots of detergent-insoluble plasma membrane fractions contained proteins recognized by antibodies to brain fodrin and erythrocyte band 4.1, whereas blots probed with antibodies to erythrocyte spectrin and ankyrin were negative. Fodrin and band 4.1 were not detected in granule fractions, but some fodrin was present in the cytosol. The association of proteins related to fodrin and band 4.1 with the plasma membrane suggests that PMNs contain a submembranous skeleton structurally analogous to that of erythrocytes and platelets. The specific function of these proteins and their structural organization in human PMNs await further study.     

Variable flip angle schedules in bSSFP imaging of hyperpolarized noble gases

Balanced steady-state free precession imaging sequences provide signal-to-noise ratio benefits for MRI of hyperpolarized nuclei. Hyperpolarized magnetization decays during the imaging sequence to thermal equilibrium, effectively necessitating imaging in a transient state characterized by nonconstant transverse magnetization and k-space filtering when using constant flip angles. This work presents an analytical method for calculation of variable flip angle schedules which maintain constant transverse magnetization in balanced steady-state free precession imaging of hyperpolarized nuclei. The approach is based on direct inversion of the Bloch equations and does not require any numerical optimization. Input parameters are pulse sequence timings and effective relaxation times, which take diffusion of hyperpolarized gas in imaging gradients into account. Provision of constant transverse magnetization is demonstrated in phantom experiments and human lung imaging using hyperpolarized (3) He. The benefit of a flat k-space filter is demonstrated by reduced blurring in (3) He and digital phantom data, and high quality (3) He ventilation images from human lungs are obtained.     

Cholesterol efflux capacity of high‐density lipoprotein was not associated with cognitive decline and brain structures in older people with diabetes mellitus

Aims/IntroductionTo examine the association between cholesterol efflux capacity (CEC) of serum high‐density lipoprotein (HDL) and cognitive function and brain structures in older people with diabetes mellitus.Materials and MethodsParticipants of a randomized placebo‐controlled trial of 27‐month vitamin B₁₂ supplementation in older people with diabetes mellitus, which showed no effect on cognition, were further followed up at month 72. Cognitive tests included the Clinical Dementia Rating scale, Neuropsychological Test Battery in memory, executive function and psychomotor speed. Brain magnetic resonance imaging scans were carried out in a subset at baseline, month 27 and month 45. Fasting serum at baseline, month 9, month 27 and month 72 were analyzed for adenosine triphosphate‐binding cassette transporter A1‐mediated CEC of HDL and apolipoprotein A1 (ApoA1).ResultsSerum HDL cholesterol at baseline was associated with better executive and memory function at follow up. Serum ApoA1 was associated with a better memory Z‐score at month 18. Serum CEC and ApoA1 were not associated with Clinical Dementia Rating scale, Neuropsychological Test Battery, hippocampal volume and white matter disease on magnetic resonance imaging at baseline and whole brain atrophy rates. They were also not associated with cognitive function at month 27 and 72 on multilevel modeling. CEC and ApoA1 decreased significantly from baseline to month 27. Faster decliners in CEC had a greater increase in brain peak width of skeletonized mean diffusivity.ConclusionsHigher serum HDL cholesterol was associated with more favorable changes in memory and executive function in older people with diabetes mellitus. However, this was not due to CEC or ApoA1. A decline in CEC was associated with small vessel disease in the brain.     

Feasibility of extension of platinum-free interval with weekly bolus topotecan and subsequent platinum retreatment outcomes in recurrent ovarian cancer

Purpose  

The goal of this study was to evaluate the outcomes and response in a cohort of patients with presumed platinum-sensitive disease who were subsequently retreated with platinum after receiving weekly bolus topotecan at the time of initial recurrence.