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Biomedical subjects

B L Miller

Publications and source records attributed to B L Miller.

At least 19 recordsLinked to original sources
PubMed1992

Neuropsychological correlates of white-matter lesions in healthy elderly subjects. A threshold effect.

The clinical significance of white-matter lesions (WMLs) detected by computed tomography and magnetic resonance imaging in healthy elderly subjects has been controversial, with some studies reporting associated deficits in cognition and others failing to document cognitive disturbance. In our sample of 100 healthy elderly individuals, almost half (n = 46) had no WMLs, approximately one fourth had minimal (less than or equal to 1 cm2; n = 27) or moderate (greater than 1 cm2 but less than or equal to 10 cm2; n = 21) WML areas, and six subjects had large WML areas (greater than 10 cm2). Substantial disturbances in basic attention and selected frontal lobe skills were detected in the six subjects with the large WML areas. These findings suggest that a "threshold" of WML area must be present before cognitive deficits are observed. Surprisingly, no significant relationships between duration of hypertension or cholesterol levels and WMLs were detected, suggesting that factors other than vascular disturbances are involved in the origin of at least some WMLs.

Aged↗
PubMed1992

Emergency room evaluation of cocaine-associated neuropsychiatric disorders.

The widespread abuse of cocaine has produced an alarming number of cocaine-related emergency room visits in the last several years. The authors discuss the various issues involved in emergency rom evaluation of patients who abuse cocaine and manifest signs and symptoms suggesting neuropsychiatric disease. Appropriate triage is emphasized, and a discussion of impediments to the accurate assessment of these patients ensues. The unique features of cocaine-induced mood, psychotic, and organic disorders are then detailed and contrasted with other functional and organic disorders. Strategies for the emergency room treatment of patients exhibiting symptomatology consistent with cocaine intoxication and withdrawal are outlined. The issues of psychiatric comorbidity and dual diagnosis in the cocaine-abusing population are examined. In addition, the neurological complications associated with the use of cocaine are reviewed. Finally, emerging data from single photon emission computerized tomography (SPECT) analysis of cocaine abusers is reported.

Brain Damage, Chronic↗
PubMed1992

StuA is required for cell pattern formation in Aspergillus.

The stunted (stuA) gene product is required for the orderly differentiation and spatial organization of cell types of the Aspergillus nidulans conidiophore. Expression of the stuA gene is complex. Two transcripts, stuA alpha and stuA beta, are initiated from separate promoters. Transcription of both RNAs increases approximately 50-fold during the establishment of developmental competence. Induction-dependent transcriptional and post-transcriptional regulatory mechanisms further enhance expression 15-fold. Consistent with the latter observation, both transcripts have structural features characteristic of RNAs subject to translational control. Conidiophore morphogenesis requires regulatory interactions between the products of the stuA, bristle (brlA), and abacus (abaA) genes. Enhanced stunted expression is cell type specific and dependent on a functional BrlA protein. StuA affects the spatial localization of AbaA by acting directly, or indirectly, to repress abaA expression.

Amino Acid Sequence↗
PubMed1992

A quantitative MRI study of vascular dementia.

We studied the MRI and clinical factors associated with dementia following stroke by quantifying ventricle-to-brain ratio (VBR), anatomic region of infarction, and cortical, subcortical, and white matter areas of infarction in 24 stroke patients with dementia and 29 nondemented stroke patients. The factors that most strongly correlated with dementia were total white matter lesion (WML) area, left WML, VBR, right WML, age, left cortical infarction area, left parietal infarction area, and total infarction area. Using discriminant analysis, these factors correctly classified 28 of 29 nondemented patients and 18 of 24 demented patients. Both cortical and white matter total infarction area measurements were strongly associated with dementia in stroke patients, suggesting that these factors strongly influenced the development of dementia following stroke. There was a strong association between dementia and left- but not right-hemisphere infarction area. The only demographic factor that strongly associated with dementia was age.

Aged↗
PubMed1992

Neuropsychiatric effects of cocaine: SPECT measurements.

Cocaine causes serious neurologic and neuropsychiatric complications. Cocaine-induced seizures are common and appear to be due to the local anaesthetic actions of this compound. Cocaine induced stroke has varied mechanisms. With ischemic stroke there is severe vasospasm induced by rises in brain catecholamines. These changes can persist for many weeks and can be demonstrated using single-photon emission computerized tomography (SPECT). In many patients with psychiatric symptoms such as psychosis or mania, SPECT demonstrates similar changes in cerebral blood flow. In fact, some of the psychiatric symptoms induced by cocaine may be due to decreases in cerebral blood flow. In cocaine abuse, treatment strategies based on decreasing cerebral vasospasm need to be developed.

Bipolar Disorder↗
PubMed1991

Studies on DNA-cleaving agents: computer modeling analysis of the mechanism of activation and cleavage of dynemicin-oligonucleotide complexes.

Dynemicin A is a recently identified antitumor antibiotic. Upon activation, dynemicin is reported to cause double-stranded cleavage of DNA, putatively through the intermediacy of a diradical. Computer modeling of this activation and cleavage process is described herein as part of an effort to establish a structural hypothesis for this mechanistic sequence and for the design of simple analogues. Intercalation complexes of duplex dodecamers [d(CGCGAATTCGCG)]2 and [d(GC)6]2 with both enantiomers of dynemicin and of all related mechanistic intermediates are evaluated. Examination of these structures shows that cycloaromatization of dynemicin to a diradical intermediate results in the rotation of the diradical-forming subunit with respect to the intercalation plane that is of an opposite sense for the two dynemicin enantiomers. In addition, the activation of the (2S) enantiomer of dynemicin occurs by a less restricted approach trajectory than the corresponding (2R) enantiomer. In all complexes, the 5'-3' strand is at least 1 A closer than the 3'-5' strand to the diyl intermediate. As a result, complexes are produced in which the diyl moiety is aligned along [(2S)] or across [(2R)] the minor groove, leading to different predictions for the selectivity of radical-initiated, oxidative lesion of DNA. Molecular dynamics simulations are found to support these predictions, including the 3-base-pair offset cleavage reported for dynemicin.

Anthraquinones↗
PubMed1991

A review of chemical issues in 1H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline.

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.

Aspartic Acid↗
PubMed1991

Isolation and transcriptional characterization of a morphological modifier: the Aspergillus nidulans stunted (stuA) gene.

The functions of at least four potential regulatory genes are known to overlap temporally during elaboration of the multicellular asexual reproductive apparatus (conidiophore) of Aspergillus nidulans. One of these, the stuA (stunted) gene, has been previously classified as a morphological modifier essential for correct spatial organization of the conidiophore. The gene was cloned by complementation of a strain carrying the stuA1 mutation and has been localized to a 5.0 kb KpnI fragment that encodes a 3.3 kb mRNA. The stuA mRNA was detected at very low levels in mature conidia and in somatic hyphae that had not established developmental competence. A dramatic increase in the abundance of this mRNA occurred coincidentally with the establishment of competence, but prior to the induction of conidiation. RNA abundance remained at this elevated level during conidiophore morphogenesis. These results are consistent with genetic data suggesting that stuA gene function is required from the very earliest events of asexual reproduction until completion of conidiophore development, but is not specifically required for differentiation of conidia. The expression of the stuA transcript was not affected by any of the other characterized developmental mutations. These latter results suggest that transcriptional activation at the onset of competence is mediated by an as yet unidentified genetic locus or loci.

Aspergillus nidulans↗
PubMed1991

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

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)

Adult↗
PubMed1991

Brain lesions and cognitive function in late-life psychosis.

Twenty-four patients who developed their first psychotic episode after the age of 45 were studied with MRI and comprehensive neuropsychological testing and compared with 72 healthy elderly subjects. The patients demonstrated more clinical abnormalities on MRI, were more likely to have large white-matter lesions or metabolic illness, and did more poorly on many neuropsychological tests, particularly those testing frontal-lobe and memory abilities. We conclude that structural brain injury is commonly associated with the late onset of psychosis. Neuroimaging investigations are a valuable component in the evaluation of this patient group.

Aged↗
PubMed1991

Frontal lobe degeneration: clinical, neuropsychological, and SPECT characteristics.

The clinical, neuropsychological, and cerebral blood flow characteristics of eight patients with frontal lobe degeneration (FLD) were studied. Social withdrawal and behavioral disinhibition were the earliest and most common clinical presentations, and psychiatric symptoms typically preceded the onset of dementia by several years. Neuropsychological testing showed selective impairment of frontal and memory tasks with relative sparing of attention, language, and visuospatial skills. Single-photon emission computerized tomography demonstrated frontal and temporal hypoperfusion with relative sparing of parietal and occipital blood flow. Previous studies suggest that the neuropathologic findings in patients with FLD are varied; some demonstrate frontal gliosis, neuronal loss, and Pick bodies while others show only gliosis and neuronal loss.

Aged↗
PubMed1991

Cocaine induced hypertensive encephalopathy.

A 40 year old chronic cocaine abuser came to hospital with a blood pressure of 260/160, headache, agitation and bilateral papilledema. She was felt to have hypertensive encephalopathy secondary to cocaine abuse. She failed to respond to initial treatment with intravenous nitroprusside alone but was responsive to additional therapy with captopril.

Adult↗