Search PubMed⌕ Search

Biomedical subjects

R A Andersen

Publications and source records attributed to R A Andersen.

At least 109 records · Page 6Linked to original sources

Induction of metallothionein production by zinc in human mononuclear cells.

1. Low mol. wt proteins with high Cd-binding capacity were found to be induced by Zn in cultured monocytes and lymphocytes. 2. In T cell cultures one protein was found to be induced by 125 microM Zn for 6 days, while in monocytes and B enriched cells under these conditions two proteins were found, of which the one with higher mol. wt had similar electrophoretic mobility to the T cell protein on polyacrylamide gels. 3. Mol. wt criteria and crossreactivity towards anti-metallothionein (Mt) antibody identified these proteins to be Mts of about 23 and 27 kDa mol. wt. 4. Metal binding studies indicated that monocyte and lymphocyte Mts had a higher affinity to Zn compared to Cd than rat liver Mt and Mts from Cd-resistant substrains of a human epithelial and a murine fibroblast cell line. 5. The presence of the T cell mitogen phytohemagglutinin (PHA) was found not to be necessary for this Mt induction by Zn.

B-Lymphocytes↗

Eye position effects on visual, memory, and saccade-related activity in areas LIP and 7a of macaque.

We studied the effect of eye position on the light-sensitive, memory, and saccade-related activities of neurons of the lateral intraparietal area and area 7a in the posterior parietal cortex of rhesus monkeys. A majority of the cells showed significant effects of eye position, for each of the 3 types of response. The direction tuning of the light-sensitive, memory and saccade responses did not change with eye position but the magnitude of the response did. Since previous work showed a similar effect for the light-sensitive response of area 7a neurons (Andersen and Mountcastle, 1983; Andersen et al., 1985b), the present results indicate that this modulating effect of eye position may be a general one, as it is found in 3 types of responses in 2 cortical areas. Gain fields were mapped by measuring the effect of eye position on the magnitude of the response at 9 different eye positions for each neuron. The gain fields were usually planar or largely planar for all 3 types of response in both areas, indicating that the magnitude of the response usually varies linearly with both horizontal and vertical eye position. A similar observation was made previously for the gain fields of the light-sensitive response of area 7a neurons (Andersen et al., 1985b). Although gain fields sloped in all directions for the population of cells, the gain field slopes of the light-sensitive, memory and saccade responses for individual cells were usually similar. It is proposed that these eye position effects play an important role in making coordinate transformations for visually guided movement.

Animals↗

Effect of storage conditions on nitrosated, acylated, and oxidized pyridine alkaloid derivatives in smokeless tobacco products.

Very large concentration increases in nitrite (34-fold), nitrosated pyridine alkaloids, and related 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (14- to 33-fold) occurred in moist snuff during storage at 24 degrees C for 52 weeks, whereas, decreases in all parent and some acylated pyridine alkaloids were observed in the same material. Nitrite concentrations in dry snuff decreased up to 90% during storage; increased contents of nitrosated alkaloids and NNK of 30 to 80% were also observed. Storage effects on chewing tobacco included a 75% increase in nitrite and small increases of nitrosated alkaloids and NNK. Sums of parent alkaloids in moist snuff decreased 24 and 54% after storage for 24 weeks at 24 and 32 degrees C, respectively, while sums of alkaloid derivatives increased, up to 36-fold for nitrosated alkaloids and NNK, 92% for acylated, and 133% for oxidized components. Levels of N'-nitrosonornicotine, NNK, and N'-nitrosoanatabine after 52 weeks' storage at 24 degrees C were 547, 41, and 296% higher, respectively, in ambient air-exposed moist snuff than in the nonexposed counterpart. A mathematical model was evaluated and used to calibrate nonlinear gas chromatography alkali bead detector response to the individual components. This permitted the use of a single analysis for all required individual compounds over a wide concentration range.

Acylation↗

Reduction of hexavalent chromium in a reconstituted system of cytochrome P-450 and cytochrome b5.

The reduction of hexavalent chromium (Cr(VI] by the monooxygenase components was studied. Both a reconstituted system of cytochrome P-450 (P-450) and cytochrome b5 (b5) with NADPH was capable of reducing Na2CrO4 (30 microM) provided anaerobic atmosphere. The rates were 1.29 nmol Cr.min-1 nmol P-450(-1) and 0.73 nmol Cr.min-1 nmol b5(-1). Using NADH instead of NADPH gave very low reducing activities, confirming the enzymic nature of the P-450 dependent Cr(VI) reductase reaction. Oxygen, 22% (air) and 0.1% gave 89% and 69% inhibition of Cr(VI) reducing activity, respectively. Carbon monoxide (100%) caused an inhibition of about 37% and 44% for P-450 and b5, respectively. Externally added flavin mononucleotide (FMN) (3 microM) or Fe-ADP (10 microM) to the complete system stimulated the enzymatic reaction about 2-fold and 3-fold, respectively.

Animals↗

Is metallothionein involved in deposition of cadmium in bile?

1. By use of our metallothionein (Mt) antibody in Western blotting and techniques for investigating protein metal-binding capacity, the form and content of Mt in bile, collected from cadmium (Cd) treated rats, were studied. 2. It was found that bile is an excretory pathway for Mt from the liver. 3. However, only immunoreactive proteins of higher molecular weight, probably representing polymerized forms of Mt or Mt bound to other proteins, were detected. 4. No monomeric Mt was found. 5. Excretion of Mt is probably not of importance in biliary metal transport.

Animals↗

Do cadmium and dexamethasone induce different types of metallothioneins?

1. Dexamethasone induced thionein in rat liver cross reacts with antibody made towards Cd-thionein from rat liver. 2. Dex-thionein binds Cd. 3. Compared to Cd-thionein, dex-thionein behaves differently on SDS polyacrylamide gels. 4. On molecular filtration on Sephadex G-75 columns, dex-thionein elutes slightly more towards the low molecular weight region than Cd-thionein. 5. Dex-thionein elutes in one peak with two shoulders after DEAE-Sephadex A-50 ion exchange chromatography, while Cd-thionein elutes in two peaks.

Animals↗

Occurrence of various forms of metallothionein in the rat after a short-term cadmium injection regimen.

1. Results are presented showing that the metal-binding metallothionein (Mt) species induced in rat liver in response to Cd administration consist of dimeric and trimeric forms of Mt. A monomeric form might be the first step in the polymerization process. 2. Two proteins (about 8 and 20 kDa mol. wt) are found in hippocampus, but not in brain cortex. 3. These proteins could not be demonstrated to cross-react with our Mt antibody, but the largest of them has strong Cd-binding capacity. 4. Our Mt antibody cross-reacts with a high metal affinity protein present in both brain cortex and hippocampus of twice the mol.wt (20 kDa) of our purified rat liver Mt standard. 5. The results indicate, however, that these Mt like proteins probably emerge from high molecular or membrane bound forms in the cells. 6. A theory is proposed that the predominant polyacrylamide gel band, matching the monomeric, rat liver Mt standard band, seen for all tissues studied in the present work originate from two sources, namely membrane bound and heavy metal induced monomeric form. 7. It is furthermore suggested that those tissues playing an active role in heavy metal metabolism and in protection against toxicity of such metals contain soluble Mts whose active metal-binding forms are oligomers.

Animals↗

A back-propagation programmed network that simulates response properties of a subset of posterior parietal neurons.

Neurons in area 7a of the posterior parietal cortex of monkeys respond to both the retinal location of a visual stimulus and the position of the eyes and by combining these signals represent the spatial location of external objects. A neural network model, programmed using back-propagation learning, can decode this spatial information from area 7a neurons and accounts for their observed response properties.

Animals↗

Perception of three-dimensional structure from motion in monkey and man.

Information on motion is important for the determination of the three-dimensional (3-D) structure of the environment for both human and non-human primates. For example, if a person were to close one eye and look at an evenly illuminated, irregularly shaped object, he would be unlikely to guess its shape correctly. But if the object is moved about, the correct shape immediately becomes apparent. Little is known about how the primate visual system actually does this, although various theories have been proposed. We have developed novel, highly controlled motion stimuli to use with psychophysical and physiological techniques to study how 3-D structure is obtained from motion. We show that the Rhesus monkey can detect 3-D structure from motion in the same way as human subjects. Furthermore, the dependence of both species on certain parameters of the display shows that information is integrated both spatially and temporally for this higher visual function.

Animals↗

Memory related motor planning activity in posterior parietal cortex of macaque.

Unit recording studies in the lateral bank of the intraparietal cortex (area LIP) have demonstrated a response property not previously reported in posterior cortex. Studies were performed in the Rhesus monkey during tasks which required saccadic eye movements to remembered target locations in the dark. Neurons were found which remained active during the time period for which the monkey had to withhold eye movements while remembering desired target locations. The activity of the cells was tuned for eye movements of specific direction and amplitude, and it was not necessary for a visual stimulus to fall within the response field. The responses appeared to represent a memory-related motor-planning signal encoding motor error. The relation of the activity to the behavior of the animal suggests that the response represents the intent to make eye movements of specific direction and amplitude.

Animals↗

Preparation of metallothionein from rat liver and studies of its properties with respect to use as a standard in gel permeation chromatography, polyacrylamide gel systems, autoradiography and Western blotting.

1. A simple method for preparation of metallothionein (Mt) I and II has been developed for the purpose of making standards for use in various biochemical systems and in antibody production. 2. The theoretical content of SH groups in a Mt protein; assuming the mol. wt to be 10,000 and each molecule to contain 20 SH groups was found to be 7.1 and 7.7 times higher than for our purified Mt I and II, respectively. 3. In our native polyacrylamide gel system Mt I ran ahead of Mt II, while the two Mt forms were not separated in the Laemmli SDS system in which it behaved as a protein with mol. wt 10,000. In both gel systems, however, Mt I stained as a very faint band in comparison to Mt II, despite equal absorbance at 254 nm and Cd binding capacity. 4. Compared to staining of polyacrylamide gels with Coomassie Brilliant Blue less than 1/50 parts (1 ng) of the protein could be easily seen after silver staining. 5. It was found that Mt may undergo spontaneous modification, polymerization and loss of metal binding properties. 6. Spontaneous modification and polymerization reduced the antigenic properties of our purified Mt. Only Mt II appeared to be immunologically active.

Animals↗

The role of the teacher in learning-based models of parietal area 7a.

The back-propagation learning procedure can be used to train simulated neural networks to compute arbitrary functions. We have recently shown that when such a network is trained to carry out the transformation of stimulus location to head-centered coordinates that occurs in parietal area 7a, the response properties of certain units in the network closely resemble neurons found in area 7a. The back-propagation procedure requires the use of a teacher. Here we examine the effect of using different kinds of teachers. As long as the teacher represents information about stimulus location in head-centered coordinates, the trained network contains units of the kind found in area 7a. Differences in teacher format only effect the quantitative distribution of the different unit types. When the teacher does not represent stimulus location explicitly, the network does not contain units of the required kind.

Computer Simulation↗

The role of the posterior parietal cortex in coordinate transformations for visual-motor integration.

Lesion to the posterior parietal cortex in monkeys and humans produces spatial deficits in movement and perception. In recording experiments from area 7a, a cortical subdivision in the posterior parietal cortex in monkeys, we have found neurons whose responses are a function of both the retinal location of visual stimuli and the position of the eyes in the orbits. By combining these signals area 7 a neurons code the location of visual stimuli with respect to the head. However, these cells respond over only limited ranges of eye positions (eye-position-dependent coding). To code location in craniotopic space at all eye positions (eye-position-independent coding) an additional step in neural processing is required that uses information distributed across populations of area 7a neurons. We describe here a neural network model, based on back-propagation learning, that both demonstrates how spatial location could be derived from the population response of area 7a neurons and accurately accounts for the observed response properties of these neurons.

Animals↗

Effects of organophosphates on presynaptic events in the vascularly perfused phrenic nerve-hemidiaphragm preparation from the rat.

A vascularly perfused phrenic nerve-hemidiaphragm preparation from the rat was developed to study effects of physostigmine and some organophosphate inhibitors on the synthesis and release of endogenous and deuterium-labelled (choline--D9) acetylcholine (ACh) as well as the presynaptic uptake of choline. Choline and ACh were determined by combined gas chromatography/mass spectrometry. Without stimulation the endogenous levels of ACh were 320 pmole/hemidiaphragm for unlabelled and less than 1 pmole/hemidiaphragm of deuterium-labelled ACh. After stimulation at 15 Hz for 1 hr, 460 pmole/hemidiaphragm of unlabelled and 15 pmole/hemidiaphragm of deuterium-labelled ACh were found. Without stimulation the release of unlabelled ACh was 6 pmole/min/hemidiaphragm and for deuterium-labelled 0.2 pmole/min/hemidiaphragm. Evoked release (15 Hz, 1 hr) was 22 pmole/min/hemidiaphragm for unlabelled and 1.8 pmole/min/hemidiaphragm for deuterium labelled ACh. During stimulation and treatment with high concentrations (10(-5)-10(-4) M) of soman, DFP and Vx the level of unlabelled endogenous ACh increased, but the level of deuterium labelled ACh decreased in the diaphragm. During stimulation and treatment with these inhibitors the release of both unlabelled and labelled ACh decreased. During treatment with high concentrations (10(-5)-10(-4) M) of sarin and physostigmine there were no changes in endogenous levels or release of unlabelled or deuterium labelled ACh. The different effects of cholinesterase inhibitors are probably linked to the synthesis and release mechanism of ACh rather than to the choline uptake mechanism.

Acetylcholine↗

Neurons of area 7 activated by both visual stimuli and oculomotor behavior.

Behavioral and clinical studies have long implicated the posterior parietal cortex of primates in spatial perception and spatially oriented behavior. However, recordings from single neurons in behaving monkeys by different laboratories have resulted in divergent views with some ascribing a largely motor and others a largely sensory role for this region. We have designed paradigms to separate the sensory and motor components of the neural activity and have found that the cells in this area respond to both sensory stimulation and motor behavior. Thus, it is likely that this area is not solely sensory or motor, but rather is involved in higher order aspects of sensory-motor integration.

Animals↗