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D L Sparks

Publications and source records attributed to D L Sparks.

At least 19 recordsLinked to original sources
PubMed1992

The conformation of apolipoprotein A-I in discoidal and spherical recombinant high density lipoprotein particles. 13C NMR studies of lysine ionization behavior.

To elucidate the molecular details of how high density lipoprotein (HDL) microstructure affects the conformation of apolipoprotein (apo) A-I in various classes of HDL particles, apoA-I structure in homogeneous recombinant HDL (rHDL) complexes containing palmitoyl-oleoyl phosphatidylcholine (POPC) and cholesteryl oleate has been investigated by NMR spectroscopy of [13C]lysine-labeled apoA-I. All Lys residues in rHDL apoA-I were labeled with 13C by reductive methylation, and then their ionization behavior was characterized by 13C NMR spectroscopy. Four discoidal particles were prepared to contain from 64 to 256 molecules of POPC and 2 molecules of apoA-I; their major diameters ranged from 9.3 to 12.1 nm. (13CH3)2-Lys resonances from apoA-I in discoidal complexes exhibit six distinct chemical shifts at pH 10. The various Lys have pKa values ranging from 8.3 to 10.5, indicating that they exist in different microenvironments. More than 80% of the Lys residues in small (9.3 nm) discoidal particles titrate at a significantly lower pH than in the large (12.1 nm) discoidal particles. This indicates that apoA-I has a different conformation on the differently size discs. Two spherical particles were prepared with POPC:cholesteryl oleate:apoA-I molar stoichiometries of 56:16:2 and 232:84:4 and diameters of 7.4 and 12.6 nm, respectively. On spherical rHDL, apoA-I (13CH3)2-Lys resonances exhibit five distinct chemical shifts at pH 10. The titration behavior of apoA-I Lys residues is the same in small and large spherical particles, indicating that apoA-I conformation is similar on the two particles. The Lys microenvironments indicate that the conformation of apoA-I in discoidal complexes is dependent on particle size and that these conformations are substantially different from that of apoA-I on spherical complexes. Lys microenvironments in discoidal complexes differ from that of spherical complexes by 4 to 5 ysines which titrate with relatively low pKa values on discs. This reflects apparent differences in conformation in the NH2-terminal one-third of apoA-I on discs and spheres.

Amino Acid Sequence↗
PubMed1992

The charge and structural stability of apolipoprotein A-I in discoidal and spherical recombinant high density lipoprotein particles.

The details of how high density lipoprotein (HDL) microstructure affects the conformation and net charge of apolipoprotein (apo) A-I in various classes of HDL particles have been investigated in homogeneous recombinant HDL (rHDL) particles containing apoA-I, palmitoyl-oleoyl phosphatidylcholine (POPC) and cholesteryl oleate. Isothermal denaturation with guanidine HCl was used to monitor alpha-helix structural stability, whereas electrokinetic analyses and circular dichroism were used to determine particle charge and apoA-I secondary structure, respectively. Electrokinetic analyses show that at pH 8.6 apoA-I has a net negative charge on discoidal (POPC.apoA-I) particles (-5.2 electronic units/mol of apoA-I) which is significantly greater than that of apoA-I either free in solution or on spherical (POPC.cholesteryl oleate.apoA-I) rHDL (approximately -3.5 electronic units). Raising the POPC content (32-128 mol/ml of apoA-I) of discoidal particles 1) increases the particle major diameter from 9.3 to 12.1 nm, 2) increases the alpha-helix content from 62 to 77%, and 3) stabilizes the helical segments by increasing the free energy of unfolding (delta GD degree) from 1.4 to 3.0 kcal/mol of apoA-I. Raising the POPC content (28-58 mol/mol of apoA-I) of spherical particles 1) increases the particle diameter from 7.4 to 12.6 nm, 2) increases the percent alpha-helix from 62 to 69%, and 3) has no significant effect on delta GD degree (2.2 kcal/mol of apoA-I). This study shows that different HDL subspecies maintain particular apoA-I conformations that confer unique charge and structural characteristics on the particles. It is likely that the charge and conformation of apoA-I are critical molecular properties that modulate the metabolism of HDL particles and influence their role in cholesterol transport.

Apolipoprotein A-I↗
PubMed1992

Movement selection in advance of action in the superior colliculus.

The primate superior colliculus contains a map of saccadic eye movements. Saccades are high-velocity eye movements to selected targets in the visual field, but little is known about the neural mechanisms responsible for target selection or the related problem of choosing a particular movement from the oculomotor repertoire. Two classes of neurons have been described in the superior colliculus which show bursts of activity before the saccade: discrete bursters display a vigorous pre-saccadic burst and prelude bursters show low-frequency activity as a prelude to burst onset. We have designed experiments to test whether prelude activity is related to saccade selection. Our tasks use a cue to specify which of two physically identical visual stimuli is the goal of an impending saccade. This cue is spatially and temporally isolated from the potential targets as well as from visual cues signalling movement initiation. Our results show that prelude activity occurs shortly after information is available for correct saccade selection and, more importantly, the activity is predictive of saccade choice. The results thus suggest that the superior colliculus participates in the process of saccade selection.

Animals↗
PubMed1992

Monoaminergic and cholinergic synaptic markers in the nucleus basalis of Meynert (nbM): normal age-related changes and the effect of heart disease and Alzheimer's disease.

Neurotransmitter markers for acetylcholine, serotonin (5-HT), and dopamine (DA) were measured in autopsied human nucleus basalis of Meynert (nbM) from nondemented individuals without heart disease (non-HD) (age range, 4-84 years; n = 77), nondemented individuals with heart disease (HD) (age range, 57-92 years; n = 23), and individuals with Alzheimer's disease (AD) (age range, 59-92 years; n = 22). No significant differences in any chemical marker were found between age-matched HD and non-HD individuals. The activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), and [3H]spiperone binding were regionally distributed within the nbM in control (non-HD) subjects less than 54 years of age. The activity of AChE, 5-[3H]HT binding, and the content of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT were regionally distributed in the nbM in non-HD, HD, and AD subjects more than 54 years of age. The binding of [3H]spiperone was regionally distributed in the nbM in HD and AD subjects more than 54 years of age, only. Activity of ChAT and AChE, content of 5-HT, 5-HIAA, and DA, binding of 5-[3H]HT, and the turnover number for DA (ratio of HVA/DA) all decreased with increasing age in the non-HD control population. The content of HVA, binding of [3H]spiperone, and the turnover number for 5-HT (ratio of 5-HIAA/5-HT) did not change with increasing age. Significant reductions in ChAT and AChE activities were found in AD nbM compared with postmortem interval- and age-matched HD and non-HD individuals. The reduction of 5-HT and 5-HIAA content and [3H]spiperone binding in individuals with AD of all ages suggests a loss of functional serotonergic innervation of the nbM. Dopaminergic synaptic markers were less affected in AD nbM, although turnover numbers for both DA and 5-HT were increased in AD. Receptor upregulation in response to presynaptic deficits did not occur for DA or 5-HT.

Acetylcholinesterase↗
PubMed1992

Amygdala cell loss and atrophy in Alzheimer's disease.

The amygdala and its subnuclei undergo severe volumetric atrophy in Alzheimer's disease (AD). To determine whether this atrophy is due to loss of neuropil, specific neuronal populations, or both, we evaluated the number, size, and packing density of neurons and glia in the cortical and magnocellular basal amygdaloid subregions. The neuropil fraction did not change with AD in either region. Despite a mean 35% increase in cell packing density in the AD amygdala, total numbers of neurons and glia within tissue sections were reduced significantly; medium and large neurons were preferentially affected. The total number of small neurons was stable in the AD sample despite sharp reductions in nuclear size, suggesting that AD also results in pronounced amygdaloid neuronal shrinkage. Differences in the degree of cell loss between the two nuclei as well as changes in glial cell numbers are discussed in relation to characteristic AD neuropathology and relevant anatomical connectivity.

Aged↗
PubMed1992

Two models for transforming auditory signals from head-centered to eye-centered coordinates.

Two models for transforming auditory signals from head-centered to eye-centered coordinates are presented. The vector subtraction model subtracts a rate-coded eye position signal from a topographically weighted auditory target position signal to produce a rate-code of target location with respect to the eye. The rate-code is converted into a place-code through a graded synaptic weighting scheme and inhibition. The dendrite model performs a mapping of head-centered auditory space onto the dendrites of eye-centered units. Individual dendrites serve as logical comparators of target location and eye position. Both models produce a topographic map of auditory space in eye-centered coordinates like that found in the primate superior colliculus. Either type can be converted into a model for transforming visual signals from retinal to head-centered coordinates.

Auditory Perception↗
PubMed1992

Down's syndrome: occurrence of ALZ-50 reactive neurons and the formation of senile plaques.

We have histopathologically investigated the hippocampal formation in 4 individuals with Down's syndrome (DS), 7 control individuals, and 3 individuals dying after being in coma 3-7 days. Adjacent sections of brain were stained by the Bielschowsky method and by ALZ-50 immunocytochemical methods. ALZ-50 immunoreactive neurons were found in each individual with DS and only in the control infants. Neither ALZ-50-immunoreactive features nor abnormal silver-positive features stained by the Bielschowsky method were found in the adolescent or young adult controls or coma patients. Diffuse form senile plaques (SP) were found only in the oldest DS individual. The data suggest that ALZ-50 reactive neurons persist during the life of an individual with DS and may precede the formation of SP.

Adult↗
PubMed1992

Ultrastructural location of major histocompatibility complex (MHC) class II positive perivascular cells in histologically normal human brain.

The expression of major histocompatibility complex (MHC) class I and II antigens was studied in surgical and postmortem brain biopsy tissue using light and electron microscopic immunocytochemistry. In addition, monoclonal antibodies directed against human macrophages (EBM11) and alpha-smooth muscle actin were applied. It is shown that blood vessel-associated MHC class II immunoreactivity in histologically normal human brain can be localized to a distinct class of cells, termed perivascular cells, which share macrophage but not smooth muscle cell antigen. This immunophenotype, the location in the perivascular space as well as the morphology, frequency and tissue distribution distinguish perivascular cells from pericytes and intraparenchymal microglia. It is suggested that MHC class II positive perivascular cells are a normal constituent of the human cerebral microvasculature. The potential role of these cells in immunological reactions occurring at the blood-brain interface is discussed.

Antibodies, Monoclonal↗
PubMed1992

Quantitative measurement of lipoprotein surface charge by agarose gel electrophoresis.

The electrophoretic mobilities of low density lipoprotein (LDL) and six pure proteins in a 0.5% agarose gel have been compared to literature electrophoretic mobility values determined by the Tiselius moving boundary method. There is a strong correlation (r = 0.99) between the electrophoretic mobilities determined by the two techniques. The electrophoretic behavior of charged particles smaller than very low density lipoproteins (VLDL) is not markedly perturbed by a 0.5% agarose matrix, and variations in mobility primarily reflect differences in particle valence and density of surface charge. Application of electrokinetic theory to derive protein and lipoprotein net charges from the electrophoretic mobilities in agarose yields a quantitative delineation of lipoprotein electrophoretic migration patterns wherein the beta mobility region comprises a surface potential range of -4.5 to -7.0 mV; the pre-beta region a range of -7.0 to -10.5 mV; the alpha mobility region a range of -10.5 to -12.5 mV and the serum albumin region a range of -12.5 to -14.0 mV. Because protein conformation and charge are critical in metabolic regulation, the agarose gel electrophoresis technique provides a valuable analytical tool that should help to elucidate further details of the structure-function relationships of serum lipoprotein particles.

Electrochemistry↗
PubMed1991

Alterations in brain monoamine oxidase activity in aging, Alzheimer's disease, and Pick's disease.

Alzheimer's disease (AD) and Pick's disease (PD) are dementing disorders of unknown origin. Monoamine oxidase (MAO) is important in the metabolism of a number of monoamine neurotransmitters. This study investigates MAO activity in aging, AD, and PD in frontal and temporal poles, nucleus basalis of Meynert (nbM), and hypothalamus. Regional variations in the activity of the two MAO forms (A and B) were found in aging, AD, and PD. Age-related increase of MAO-B was found in all four areas of the brain, and MAO-A was increased in the nbM and temporal pole. In AD, MAO-B was decreased in the nbM and increased in the temporal pole, while MAO-A was increased in the hypothalamus and frontal pole. In PD, MAO-B was decreased in the nbM and increased in the hypothalamus, while MAO-A was increased in the hypothalamus and decreased in the nbM and temporal pole. These data indicate that with regard to MAO activity, AD and PD are dissimilar diseases and neither strictly follows age-related changes.

Aged↗
PubMed1991

Altered serotonergic and cholinergic synaptic markers in Pick's disease.

Choline acetyltransferase and acetylcholinesterase activities as well as serotonin and imipramine binding were determined in the hypothalamus, nucleus basalis of Meynert, and frontal and temporal poles of subjects with Pick's disease. Choline acetyltransferase activity was decreased in the hypothalamus and nucleus basalis of Meynert, and acetylcholinesterase activity was decreased in the nucleus basalis of Meynert only. Serotonin binding was decreased in all sites but the nucleus basalis of Meynert, and imipramine binding was altered only in the frontal pole. Comparison with previous reports of Alzheimer's disease indicates that with respect to these synaptic markers, Alzheimer's disease and Pick's disease are not similar.

Acetylcholinesterase↗
PubMed1991

Increased ALZ-50-reactive neurons in the brains of SIDS infants: an indicator of greater neuronal death?

Brain tissue from 15 infants who had died from sudden infant death syndrome (SIDS) and 15 age-matched control infants was investigated for the presence of degenerating neurons using ALZ-50 immunocytochemical methods. Significantly increased numbers (P less than .0001) of ALZ-50-reactive neurons were found in SIDS infants compared to infants dying of known causes. The location and appearance of such ALZ-50-reactive neurons in SIDS may indicate that the initial degeneration of the central nervous system occurs early in the development of affected infants.

Antibodies, Monoclonal↗
PubMed1991

Sudden infant death syndrome: altered aminergic-cholinergic synaptic markers in hypothalamus.

Alterations of sleep are reported to occur in sudden infant death syndrome (SIDS). It is well established that the hypothalamus mediates the onset, maintenance, and timing of sleep, and does so via serotonergic and cholinergic mechanisms. We have investigated serotonergic and cholinergic synaptic markers in the hypothalamus from eight SIDS infants and six age-matched non-SIDS infants between 3 and 7 months of age. By use of established methods, we observed a number of chemical alterations in SIDS hypothalamus: (1) tryptophan content was increased and serotonin content was decreased, (2) serotonin binding was increased and imipramine binding was unchanged, (3) monoamine oxidase-A activity was increased without an effect on monoamine oxidase-B, and (4) choline acetyltransferase activity was decreased and acetylcholinesterase activity was unchanged.

Acetylcholinesterase↗
PubMed1990

Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: effect of age and Alzheimer's disease.

Melatonin and 5-methoxytryptophol (ML) were measured in human pineals (38 controls, 16 subjects with Alzheimer's disease). Time of death had a major influence on the indole concentrations with significantly higher melatonin levels occurring at night (22.00-10.00 h) and significantly higher ML levels occurring during the day (10.00-22.00 h). This daily variation disappeared in both the older subjects (55-92 years) and in the Alzheimer patients (55-89 years).

Adolescent↗
PubMed1990

Altered pineal serotonin binding in some suicides.

Serotonergic abnormalities have been regularly reported in the brains of suicide victims. Because of evidence that pineal function is altered in depressed subjects and that serotonin-releasing axons may innervate the pineal, we assayed tritiated serotonin binding in a series of control and suicide pineals. High affinity binding was present, and there were apparent differences between some suicides and controls.

Adult↗
PubMed1990

Cerebellotectal pathways in the macaque: implications for collicular generation of saccades.

The cerebellum is thought to modulate saccadic activity in the primate in order to maintain targeting accuracy, and the cerebellotectal pathway has been posited to play a role in this modulation. However, anatomical descriptions of this pathway in primates are sketchy and conflicting. To determine whether the organization of the cerebellotectal projection in primates is similar to that found in other species, neuroanatomical tracer transport techniques were utilized in two species of macaque monkey to label cerebellotectal somata and fiber terminations. Two pathways were found. One, the fastigiotectal pathway, is derived from cells in the caudal fastigial nucleus and projects bilaterally to the rostral end of the intermediate gray layer. The other pathway is derived from cells in the posterior interposed nucleus and the adjacent posterior wing of the dentate nucleus, and it terminates contralaterally throughout the ventral half of the intermediate gray and the deep gray layers. Both of these pathways terminate within the layers of the superior colliculus containing premotor, saccade-related neurons, but the differences in the distribution of their terminals and cells of origin suggest that these two pathways have different functions. Furthermore, the pattern of connections of these two pathways indicates that they do not function as a traditional feedback circuit. We suggest that the cerebellotectal pathways may instead modulate collicular activity in a more complex manner. For example, it may provide signals necessary for corrective saccades or for maintaining spatial registry between the different sensory representations supplied to the superior colliculus and its presaccadic output, which is organized into a motor map.

Animals↗
PubMed1990

The perihypoglossal projection to the superior colliculus in the rhesus monkey.

The projection of the perihypoglossal (PH) complex to the superior colliculus (SC) in the rhesus monkey was investigated using the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Following physiological identification by electrical stimulation and multiunit recording, small injections of the tracer were placed within the SC of three monkeys. The largest numbers of retrogradely labeled neurons within the PH complex were found in the contralateral nucleus prepositus hypoglossi (NPH), in the laterally adjacent medial vestibular nucleus, and in the ventrally adjacent reticular formation (the nucleus reticularis supragigantocellularis). These labeled neurons are strikingly heterogeneous in size and morphology. The nuclei supragenualis and intercalatus also contain numerous labeled neurons in the 2 cases in which the injections involve the caudal SC. Large numbers of retrogradely labeled neurons as well as anterogradely transported WGA-HRP are observed also throughout the pontine and medullary reticular formation, including the midline raphe. The PH complex, particularly the NPH, is known to be involved in the coding of eye position and has been hypothesized to be a critical component of the "neural integrator." Our data demonstrate the existence of a robust projection from the PH complex to the contralateral SC in the rhesus monkey. This projection may serve as the anatomical substrate by which a corollary of eye position could reach the SC. Such a signal is a prerequisite for the computation, at the collicular level, of saccadic motor error signals observed in the SC of rhesus monkeys.

Animals↗