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Biomedical subjects

M Godschalk

Publications and source records attributed to M Godschalk.

13 recordsLinked to original sources

Glucocorticoids decrease vitamin D receptor number and gene expression in human osteosarcoma cells.

The mechanisms by which glucocorticoids (GC) inhibit some actions of vitamin D [1,25-(OH)2D3] are not well understood, but there is growing evidence that GC alter vitamin D receptor (VDR) number. We studied the effects of dexamethasone (DEX) on VDR number and mRNA in the human osteosarcoma cell line, MG-63. The effects of DEX on 1,25-(OH)2D3 binding were examined by incubating confluent cells overnight in media without or with 10(-6) M DEX. DEX decreased VDR number (B max) by approximately 70% (110 versus 32 fmol/mg cellular protein, p less than 0.001) without significantly changing the apparent affinity (K'D) of 1,25-(OH)2D3 for its receptor (3.8 versus 2.2 x 10(-10) M, p greater than 0.05). Overnight incubation of MG-63 cells with DEX produced a time- and dose-responsive decrease in VDR mRNA compared to untreated controls (p less than 0.01). To determine the mechanism of the DEX-mediated decrease in VDR mRNA, the effect of DEX on VDR mRNA stability was studied. We found that the half-life for the VDR mRNA was approximately 5.7 h and was not significantly changed when the cells were incubated with DEX (approximately 6.3 h). We conclude that DEX decreases both VDR number and mRNA in MG-63 osteosarcoma cells. Since the half-life of VDR mRNA was not significantly modified by dexamethasone, glucocorticoids appear to decrease VDR mRNA by inhibiting VDR gene transcription or by affecting the processing of VDR mRNA.

Actins

Replantation of the radial side of the hand in the rhesus monkey: anatomical and functional aspects. A preliminary study to composite tissue allografting.

Before human hand transplantation can even be considered, an appropriate research model must be studied in a non-human primate. The first ray of the hand, augmented with a radial forearm flap, was chosen as a functional composite tissue graft. Four technically successful replantation of the radial unit have been carried out. One monkey died on the first post-operative day due to cardiac arrythmia. Normal wound healing occurred in the other three animals. In three monkeys, functional sensory and motor recovery was almost complete. The monkeys were able to pick up small particles of food with the index finger and thumb. It is suggested that this model could be used for allogeneic composite tissue transplantation in a non-human primate.

Animals

Learning-dependent neuronal activity in the premotor cortex: activity during the acquisition of conditional motor associations.

It has been proposed that the premotor cortex plays a role in the selection of motor programs based on environmental context. To test this hypothesis, we recorded the activity of single neurons as monkeys learned visuomotor associations. The hypothesis predicts that task-related premotor cortical activity before learning should differ from that afterward. We found that a substantial population of premotor cortex neurons, over half of those adequately tested, showed the predicted learning-dependent changes in activity. The present findings support a role for premotor cortex in motor preparation, generally, and suggest a specific role in the selection of movements on the basis of arbitrary associations.

Animals

Eye-movement representation in the frontal lobe of rhesus monkeys.

We systematically explored the frontal eye field (FEF), the supplementary eye field (SEF), and nearby regions of the frontal cortex to establish the limits of these or possible adjacent eye-movement fields in macaque monkeys. We found a medio-laterally oriented band of saccadic eye-movement sites that extended from the inferior limb of the arcuate sulcus onto the medial surface of the hemisphere and into the dorsal bank of the cingulate sulcus. Two parts of this region may be outside previously described eye-movement areas. We conclude that eye movements are more broadly represented in the frontal lobes than previously described: either the SEF extends into the dorsal bank of the cingulate sulcus and laterally to the arcuate sulcus, or there are more than two frontal eye-movement fields.

Animals

Preparation of visually cued arm movements in monkey. Involvement of inferior parietal cortex.

Single-unit activity was recorded in monkey inferior parietal lobule (IPL) during performance of a visually cued limb motor task. Many neurons in the IPL modulated their activity just after the visual cue was presented, similar to the neuronal activity observed in the premotor cortex in a previous experiment. It is suggested that IPL neurons are involved in preparation of visually cued limb movement. The present results are discussed in view of a possible role for IPL and premotor cortex in processing visual information for use by the primary motor area.

Animals

Slow wave sleep and a state resembling absence epilepsy induced in the rat by gamma-hydroxybutyrate.

The effect of gamma-hydroxybutyrate (GHB) in relatively low doses (12.5--200 mg/kg) on sleep stages, electrocorticogram (ECoG) patterns and behavior was investigated in the rat. 50-100 mg/kg GHB induced slow wave sleep but, in contrast to the cat, not paradoxical sleep. 200 mg/kg induced a hypersynchronous, bilaterally symmetrical ECoG pattern, which was different in amplitude and frequency distribution from normally occurring high amplitude patterns. When the hypersynchrony occurred in bursts, the rats displayed a sudden arrest of motor behavior. Convulsions were not induced. The results, together with the finding of others that GHB is a natural constituent of mammalian brain and our previous observation that the GHB-induced hypersynchrony can be antagonized by anti-absence (anti-petit mal) drugs are discussed in view of the possibility that GHB might play a role in the etiology of absence epilepsy in man.

Animals

The role of dopaminergic systems in gamma-hydroxybutyrate-induced electrocorticogram hypersynchronization in the rat.

The effects of dopaminergic agonists and antagonists on the duration of hypersynchronization induced in the electrocorticogram (ecog) by gamma-hydroxybutyrate (gamma-HB) were tested in rats. Apomorphine (0-2-8 mg kg-1), piribedil (2-5-10 mg kt-1) and haloperidol (0-5-1 mg kg-1) had no influence on the duration of the hypersynchrony. Amphetamine (1-5-6 mg kg-1) inhibited the hypersynchrony, while (3,4-dihydroxyphenylamino)-2-imidazoline (DPI; 5, but not 1, mg kg-1) prolonged its duration. The lack of effect of the dopamine receptor agonists apomorphine and piribedil, and the dopamine receptor blocker haloperidol, on the gamma-HB-induced hypersynchrony might indicate that the inhibition of the impulse flow in the nigrostriatal dopamine system by gamma-HB is not involved in the generation of the hypersynchrony. DPI is thought to be an agonist at a dopamine receptor not sensitive to apomorphine, and its facilitatory effect on gamam-HB-hypersynchrony can be interpreted in terms of a possible involvement of another dopamine system in the ecog hypersynchrony induced by gamma-HB. The antagonism of gamma-HB by amphetamine is possibly due to an indirect stimulatory effect on noradrenergic receptors.

Amphetamine

Effect of clozapine on the sleep pattern in the rat.

The effect of clozapine on the sleep pattern in the rat was studied after a single injection (2.5--20 mg/kg) and after daily administration for 11 consecutive days (2 X 20 mg/kg/day). After a single injection clozapine significantly suppressed REM sleep in a dose-related way, leaving slow wave sleep (SWS) unchanged. Follwing chronic administration, however, clozapine exerted its most prominent effect on SWS, the enhancement of which persisted for at least 3 days after discontinuation of treatment. REM sleep decreased with the development of tolerance and in the absence of rebound phenomena. The results are discussed in the light of disturbances in brain monoamines and the tolerance these amines developed to repeated administration of clozapine.

Animals

The drinking response of the chicken to peripheral and central administration of angiotensin II.

Intravenous injection of Ang II (val5 angiotensin II amide) elicited an immediate drinking response in the domestic fowl which lasted at least 20 minutes. The minimal dosage needed was 300 mug. Intracranial injection of 10 mug Ang II through cannulas implanted in the anterior diencephalon caused a significant increase in water intake. The minimal intracranial dosage of Ang II which evoked drinking was 2.5 mug. Intracranial injection of isotonic KCl inhibited the drinking response induced by intravenously injected Ang II when administered simultaneously. This suggests that drinking caused by both intravenous or intracranial injection of Ang II is activated through identical brain regions. The positive drinking response of the chicken is repeated concecutive intracranial injections of Ang II declined from the first injection through the following ones.

Angiotensin II

The involvement of monkey premotor cortex neurones in preparation of visually cued arm movements.

Some neurones in macaque postarcuate premotor area modulate their firing frequency in relation to motor tasks which require visual information. We previously reported that a large proportion of these neurones modulate during execution of a detour reaching task in which the movement phase was separated in time from the phase in which the monkey received a visual cue for the movement required to retrieve a food reward. A large proportion of task-related neurones (75%) modulated during this 'visual' phase, in which no task-related movements were made. This modulation was related to the position of the food reward, which served as the visual cue. Most of these neurones were located in cortical area 6, close to the arcuate curvature and its spur, but also more caudally in area 4 and rostrally in area 8. In the present chronic recording experiments in monkeys, several variations of the original task were used in order to test whether the 'visual'-related neuronal modulation could be involved in preparation of the upcoming movement. This modulation is unlikely to be related to any eye or arm movements occurring during the visual phase or to changes in environmental illumination. Neither can it be related to the presence of the visual cue in a particular part of the visual field, since the pattern of neuronal modulation was similar when a cue with a fixed position was used. This modulation was, however, contingent upon the occurrence of food retrieval during the subsequent 'movement phase', since it was abolished or diminished during presentation of a 'food-reward' which the monkey did not retrieve. For several neurones, modulation pattern during the visual phase depended on whether the food reward was to be retrieved with a gross hand movement or with relatively independent finger movements. It is likely, therefore, that neurones in the postarcuate premotor cortex are involved in preparation for arm movements with the help of visual cues. The results are discussed in view of corticocortical pathways which might be involved in transmission of visual information from visual areas through parietal association areas and premotor cortex to the primary motor cortex.

Animals