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Biomedical subjects

D L Benson

Publications and source records attributed to D L Benson.

32 records · Page 2Linked to original sources
PubMed1994

Nonlinear diffusion of a growth inhibitory factor in multicell spheroids.

A mathematical model is presented for the production of a growth inhibitory factor (GIF) within a multicell spheroid. The model is based on the assumption that the GIF diffuses within the spheroid in a nonlinear spatially dependent manner. This is in contrast with previous models, in which the nonlinearity was assumed in the production term. The results of the new model are compared with those of previous models and with experimental data.

Animals↗
PubMed1994

Alpha calcium/calmodulin-dependent protein kinase II selectively expressed in a subpopulation of excitatory neurons in monkey sensory-motor cortex: comparison with GAD-67 expression.

In situ hybridization histochemistry and immunocytochemistry, including double immunofluorescence, were used to study the populations of neurons expressing the alpha subunit of type II calcium/calmodulin-dependent protein kinase (CAM II kinase-alpha) or glutamic acid decarboxylase (GAD) in the somatic sensory and motor areas of the macaque monkey cerebral cortex. Sections were subjected to in situ hybridization using radioactive, complementary RNA probes specific for monkey CAM II kinase-alpha or 67 kDa GAD mRNAs. Others were stained immunocytochemically for CAM II kinase-alpha and/or GABA. CAM II kinase-alpha and GAD-67 are expressed in different populations of cells, with no colocalization. CAM II kinase-alpha is expressed in pyramidal cells of layers II-VI, especially layers II and III, as well as in certain small nonpyramidal cells of layer IV in areas 3a, 3b, 1, and 2 and of middle regions of area 4. Both cell types produce excitatory amino acid transmitters. Therefore, as in subcortical regions, CAM II kinase-alpha will be found on the presynaptic side of excitatory synapses but on the postsynaptic side only when these synapses occur on excitatory neurons in the sensory-motor cortex. Quantitative examination showed that CAM II kinase-alpha immunoreactive cells form, on average, approximately 50% of the total neuronal population in each area, while GABA immunoreactive or GAD cRNA hybridized cells form approximately 25-30%. Thus, CAM II kinase-alpha expressing cells cannot account for the total population of non-GABAergic cortical cells, and a certain proportion of the pyramidal cells probably do not express it. In other cortical areas, gene expression for the two molecules is regulated by afferent activity. Therefore, the present results form a necessary basis for studies aimed at determining the role of activity-dependent changes in the balance of excitation and inhibition as a mechanism underlying plasticity of representational maps in the primate sensory-motor cortex.

Animals↗
PubMed1992

Developmental expression of brain derived neurotrophic factor mRNA by neurons of fetal and adult monkey prefrontal cortex.

In situ hybridization histochemistry with labeled cRNA probes complementary to monkey brain derived neurotrophic factor (BDNF) mRNAs has been used to study the cellular localization and expression of this neurotrophin in the prefrontal cerebral cortex of fetal and adult monkeys. Expression could not be detected in prefrontal cortex before the 121st fetal day. Thereafter, in fetal life and in adulthood BDNF mRNA could be detected primarily in large, putative pyramidal cells of layers III and VI throughout the prefrontal cortex. The temporal course and cellular localization of BDNF expression suggests its association with the development and stabilization of specific connections in regions of cortex that display marked functional plasticity.

Aging↗
PubMed1992

Contrasting patterns in the localization of glutamic acid decarboxylase and Ca2+/calmodulin protein kinase gene expression in the rat central nervous system.

The expression of the genes encoding the alpha subunit of type II calcium calmodulin-dependent protein kinase (CaM II kinase alpha) and the 67,000 mol. wt form of glutamic acid decarboxylase was examined throughout the rat central nervous system. In situ hybridization histochemistry, using cRNA probes, revealed a dense population of CaM II kinase alpha-expressing cells throughout the telencephalon and diencephalon. CaM II kinase alpha mRNA was also expressed in the midbrain, cerebellum and medulla oblongata, but at greatly reduced levels. No CaM II kinase alpha gene expression was detected in nuclei producing monoamines or acetylcholine. By contrast, the glutamic acid decarboxylase gene was moderately to highly expressed throughout the central nervous system. In several regions there was a complementarity in the distributions of cells expressing the glutamic acid decarboxylase or CaM II kinase alpha genes. Cells in certain nuclei such as the thalamic reticular nucleus or globus pallidus showed glutamic acid decarboxylase gene expression only; others such as the majority of the dorsal thalamic nuclei showed CaM II kinase alpha gene expression only. Several regions contained both glutamic acid decarboxylase and CaM II kinase alpha expressing cells. However, simultaneous immunostaining for both proteins revealed only two regions where CaM II kinase alpha and glutamic acid decarboxylase immunoreactivity were colocalized: the cerebellar Purkinje cells and the commissural nucleus of the stria terminalis. The results imply that CaM II kinase alpha is primarily expressed in non-GABAergic neurons. In several regions CaM II kinase alpha mRNA is concentrated in nuclei known to contain populations of neurons that use excitatory amino acid transmitters.

Animals↗
PubMed1992

Dendritic localization of type II calcium calmodulin-dependent protein kinase mRNA in normal and reinnervated rat hippocampus.

In situ hybridization histochemistry has revealed a diffuse distribution of the alpha subunit of type II calcium calmodulin-dependent protein kinase (CaM II kinase alpha) mRNA in the neuropil of regions containing CaM II kinase alpha-expressing cells and has led some to propose that it may be expressed in dendrites. In order to determine if CaM II kinase alpha mRNA is expressed in dendrites and if the gene encoding CaM II kinase alpha is regulated in response to synaptic reinnervation, we examined its expression in the hippocampus of normal rats, of rats that had received a unilateral injection of kainic acid and of rats with a unilateral entorhinal cortex lesion. The relatively specific elimination of the CA3 pyramidal cells by kainate lesions precisely correlated with the loss of CaM II kinase alpha cRNA hybridization in the stratum radiatum as well as the stratum pyramidale. Following entorhinal cortex lesions, during the period of new synapse formation in the dentate gyrus, there was no detectable change in the level of CaM II kinase alpha gene expression. These data suggest that CaM II kinase alpha mRNA is expressed in the dendrites of hippocampal pyramidal cells and, therefore, is likely to be expressed in dendrites in other regions of the central nervous system exhibiting CaM II kinase alpha cRNA labeling in the neuropil. However, changes in expression were not found to accompany new synapse formation.

Animals↗
PubMed1991

In situ hybridization reveals VIP precursor mRNA-containing neurons in monkey and rat neocortex.

The cDNAs encoding monkey vasoactive intestinal polypeptide (VIP) and PHM-27 and rat VIP and PHI-27 were cloned and used to generate antisense RNA probes. Using in situ hybridization, neurons expressing the VIP/PHM or VIP/PHI precursor mRNAs were localized in monkey and rat somatic sensory and visual cortex. In both neocortical areas of both species, labeled cells were observed in all 6 layers as well as the subcortical white matter.

Amino Acid Sequence↗
PubMed1991

Differential gene expression for glutamic acid decarboxylase and type II calcium-calmodulin-dependent protein kinase in basal ganglia, thalamus, and hypothalamus of the monkey.

In situ hybridization histochemistry, using cRNA probes, revealed a complementarity in the distributions of cells in the basal ganglia, basal nucleus of Meynert, thalamus, hypothalamus, and rostral part of the midbrain that showed gene expression for glutamic acid decarboxylase (GAD) or the alpha-subunit of type II calcium-calmodulin-dependent protein kinase (CAM II kinase-alpha). Cells in certain nuclei such as the thalamic reticular nucleus, globus pallidus, and pars reticulata of the substantia nigra show GAD gene expression only; others in nuclei such as the basal nucleus of Meynert, medial mamillary nuclei, and ventromedial hypothalamic nuclei show CAM II kinase-alpha gene expression only. A few nuclei, for example, the pars compacta of the substantia nigra and the greater part of the subthalamic nucleus, display gene expression for neither GAD nor CAM II kinase-alpha. In other nuclei, notably those of the dorsal thalamus, and possibly in the striatum, GAD- and CAM II kinase-expressing cells appear to form two separate populations that, in most thalamic nuclei, together account for the total cell population. In situ hybridization reveals large amounts of CAM II kinase-alpha mRNA in the neuropil of most nuclei containing CAM II kinase-alpha-positive cells, suggesting its association with dendritic polyribosomes. The message may thus be translated at those sites, close to the synapses with which the protein is associated. The in situ hybridization results, coupled with those from immunocytochemical staining for CAM II kinase-alpha protein, indicate that CAM II kinase-alpha is commonly found in certain non-GABAergic afferent fiber systems but is not necessarily present in the postsynaptic cells on which they terminate. It appears to be absent from most GABAergic fiber systems but can be present in the cells on which they terminate. This suggests that the kinase may be differentially engaged in pre- and postsynaptic functions at certain synapses.

Animals↗
PubMed1991

Differential effects of monocular deprivation on glutamic acid decarboxylase and type II calcium-calmodulin-dependent protein kinase gene expression in the adult monkey visual cortex.

Increases in immunocytochemically detectable type II calcium-calmodulin-dependent protein kinase (CaM II kinase) and decreases in immunocytochemically detectable glutamic acid decarboxylase (GAD) are known to occur in the visual cortex of adult monkeys following brief periods of monocular visual deprivation. In the present study, GAD and CaM II kinase gene expression was investigated under these conditions. The polymerase chain reaction (PCR) was used to generate species-specific cDNA clones that were used to make antisense RNA probes. A second form of CaM II kinase alpha, CaM II kinase alpha-33, which contains an additional phosphorylation consensus sequence, was identified. In situ hybridization in normal visual cortex revealed a complex sublaminar organization of GAD-expressing cells within layers IVC and VI and a distribution of CaM II kinase alpha-expressing cells that was greatest in layers II, III, IVB, and VI. In situ hybridization in the cortex from animals that had been monocularly deprived revealed enhanced CaM II kinase mRNA levels in deprived-eye columns of layer IVC and, associated with the deprived eye, cytochrome oxidase-stained periodicities in other layers. In layer IV, the enhancement of labeling in deprived-eye stripes was, on average, 16% greater than in normal-eye stripes. By contrast, GAD, mRNA levels appeared unchanged in all layers, suggesting a posttranscriptional regulatory mechanism.

Amino Acid Sequence↗
PubMed1989

Expression of glutamic acid decarboxylase mRNA in normal and monocularly deprived cat visual cortex.

Neurons expressing glutamic acid decarboxylase (GAD) mRNA were localized by in situ hybridization in normal and monocularly deprived cat visual cortex by using single-stranded RNA probes transcribed from cDNAs cloned in vectors with the T3 and T7 RNA polymerase promoters. In Northern blot analyses, these RNA probes identified 2 forms of GAD mRNA, one of which is approximately 200 bases longer than the other which has previously been identified. The distribution of neurons containing GAD mRNA was compared with the distribution of immunocytochemically identified GABA neurons and in both cases the highest density of labeled neurons was found in layers II, III, and upper VI. All other cellular layers contained a homogeneous, but lower density of labeled cells. Cells expressing GAD mRNA outnumbered GABA immunostained neurons by approximately 10%, but colocalization of GAD mRNA with GABA immunocytochemistry revealed that the two methodologies were detecting the same neuronal population. To determine whether decreased retinal activity affected the levels of GAD mRNA in adult cats, neurons containing GAD mRNA were counted in normal and monocularly deprived visual cortex. However, the number of cells expressing GAD mRNA did not change following monocular deprivation.

Animals↗
PubMed1987

A monoclonal antibody to non-phosphorylated neurofilament protein marks the vulnerable cortical neurons in Alzheimer's disease.

Various cytoskeletal proteins have been implicated in the formation of neurofibrillary tangles in Alzheimer's disease. A monoclonal antibody to non-phosphorylated neurofilament protein labels a distinct subset of pyramidal cells in the normal human cortex which have a distribution very similar to that of neurofibrillary tangles in brains from patients with Alzheimer's disease. In addition, regions and layers that normally contain a high density of such cells, in Alzheimer's disease, have large numbers of neurofibrillary tangles and few remaining immunoreactive cells.

Aged↗
PubMed1977

Isolation and spectral characteristics of the photochemical reaction center of Rhodopseudomonas viridis.

A method is described for isolation of the Rhodopseudomonas viridis reaction center complex free of altered, 685 nm absorbing pigment. This improved preparation contains two c-type cytochromes in the ratio P-960: cytochrome c-558: cytochrome c-553 of 1:2:2 to 3. The near infrared spectral forms of the reduced preparation are located at 790, 832, 846, and 987 nm at 77 K; the oxidized complex absorbs at 790, 808, 829 and approx. 1310 nm. The 790 nm band is attributed to bacteriophaeophytin b and the other absorbances to bacteriochlorophyll b, The visible absorption bands may be assigned to these pigments and to the cytochromes present and, probably to a carotenoid. The presence of two bacteriochlorophyll b spectral forms in the P+-830 band suggests that exciton interactions occur among pigments in the oxidized, as well as the reduced, reaction center. Changes in the 790 and 544 nm bands upon illumination of the reaction center preparation at low redox potential may be indicative of a role for bacteriophaeophytin b in primary photochemical events.

Bacteriochlorophylls↗
PubMedDate not supplied

Activity-dependent changes in GAD and preprotachykinin mRNAs in visual cortex of adult monkeys.

Tachykinin-immunoreactive neurons are a subgroup of the GABA neuronal population in layer IVC of monkey primary visual cortex. Following brief periods of monocular deprivation in adult monkeys, immunoreactivity for both GABA and tachykinins is dramatically reduced in layer IV cells that lie within the deprived ocular dominance columns of this cortical area. The present study shows that these activity-dependent changes are associated with changes in mRNA levels but over different time courses. Radioactive antisense riboprobes derived from monkey-specific cDNAs were used to localize glutamic acid decarboxylase (GAD) and beta-preprotachykinin (beta PPT) mRNAs by in situ hybridization histochemistry. GAD and beta PPT mRNAs decreased in deprived ocular dominance columns of adult monkeys when neural activity was abolished in one eye by intraocular injections of tetrodotoxin (TTX). beta PPT mRNA levels fell within 5 d of deprivation and thus appeared to parallel the fall in immunodetectable tachykinin levels. By contrast, reduced GAD mRNA levels were detectable only after 15 d of deprivation and long after the fall in immunoreactive GAD and GABA levels has maximized. These results suggest that tachykinin gene expression is regulated by transcriptional mechanisms as part of the first response to reduced neural activity whereas the initial downregulation of immunoreactive GAD and GABA depends on posttranscriptional mechanisms. Following a more prolonged period of deprivation, a secondary mechanism for GAD regulation appears to be engaged at the level of gene transcription or possibly by changes in mRNA stability.

Animals↗