Showing papers by "Bruce L. Miller published in 1991"

A review of chemical issues in 1H NMR spectroscopy: N‐acetyl‐l‐aspartate, creatine and choline

Abstract: The structure and function of the chemicals contributing to the three main peaks seen with 1H NMR spectroscopy, N-acetyl-L-aspartate (NAA), creatine/phosphocreatine (Cr), and choline-containing compounds (Cho) is reviewed and the changes seen with these compounds in various disease states are briefly outlined. NAA is present within neurons although its biological function is largely unknown. NAA is elevated in several degenerative neurological conditions including amyotrophic lateral sclerosis and canavan disease, and in high concentrations it may behave like a neurotoxin. The creatine peak seen with 1H NMR spectroscopy consists of creatine and phosphocreatine which serve as a reserve for high-energy phosphates in the cytosol of muscle and neurons. They also buffer cellular ATP/ADP. The Cho peak seen with 1H NMR consists of a complex mixture of Cho-containing compounds. Cho is a precursor for the neurotransmitter acetylcholine and for the membrane constituent phosphatidylcholine. Future studies of changes seen in the Cho peak with stroke, degenerative dementia, drug intake, and infectious and neoplastic brain masses will be of great interest.

Brain injury and cognitive function in late-onset psychotic depression.

Abstract: Fourteen patients who developed a psychotic depression after age 45 were compared with 72 non-psychiatrically ill elderly control subjects using neuroimaging and neuropsychological (NP) tests. Despite the fact that the patients were not studied if they had an obvious dementia or neurological disease, structural brain abnormalities were found in approximately two-thirds of patients and in less than 10% of controls. The most common abnormality, subcortical white matter (WM) lesions, was thought to be vascular in etiology. Also, tumor and primary degenerative dementia were found more frequently in the patients. Compared to an age-, sex-, and education-matched control group, the patients performed more poorly on NP tests of frontal lobe, memory, and visual spatial abilities. Diagnostic evaluation of the patient with late-onset psychotic depression should include computed tomography or magnetic resonance imaging as structural brain abnormalities are common in these patients.

Measurement of amyloid peptide precursor of Alzheimer disease in human blood by double antibody immunoradiometric assay.

Abstract: The dementia of Alzheimer disease (AD) correlates with the deposition of extracellular amyloid, and this amyloid arises from the abnormal processing of a high molecular weight amyloid peptide precursor (APP), which is a normal cellular protein that is found in both brain and in peripheral tissues in humans. Overproduction of the APP in AD could cause increased concentrations of this protein in either human blood or cerebrospinal fluid (CSF). However, thus far no direct demonstration of soluble APP in human blood has been possible, owing to poor assay sensitivity and interfering plasma proteins. These two problems were eliminated with the present development of an extracting two-site immunoradiometric assay (IRMA). Two rabbit polyclonal antisera were prepared reacting to two different sites (amino acids 161-180 and 597-624) of the APP molecule. The near N-terminal antiserum (anti-APP161-180) was covalently coupled to a solid phase support and the near C-terminal directed antiserum (anti-APP597-624) was indirectly labeled using 125I-labeled near C-terminal synthetic peptide corresponding to amino acids 597-624. The IRMA was validated by partial purification of the APP from human serum and demonstration of the protein's molecular weight (112 kDa) by Western immunoblot procedures. Results of the IRMA showed that the APP is present in human plasma (mean +/- SE concentration = 32 +/- 6 pM, n = 25), and there was no significant difference in the APP concentration in 25 controls, 19 patients with AD, and 10 individuals with Down syndrome (DS). Immunoreactive APP was generally not detectable in control or AD CSF volumes as large as 1 ml.(ABSTRACT TRUNCATED AT 250 WORDS)