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Biomedical subjects

J Nielsen

Publications and source records attributed to J Nielsen.

At least 235 records · Page 13Linked to original sources
PubMed1995

Growth-dependent translation of IGF-II mRNA by a rapamycin-sensitive pathway.

Insulin-like growth factor (IGF)-II is important for fetal growth and development. The human IGF-II gene generates multiple mature transcripts with different 5' untranslated regions (5'UTRs) but identical coding regions and 3'UTRs. We have previously shown that a minor 4.8-kilobase messenger RNA was engaged in the synthesis of preproIGF-II, and a major 6.0-kb mRNA was untranslated and stored in a 100S ribonucleoprotein particle. Here we demonstrate that the 6.0-kb mRNA is selectively mobilized and translated in dispersed exponentially growing cells. Translational activation is prevented by rapamycin and mimicked by anisomycin, which suggests that translation of the 6.0-kb mRNA is regulated by the p70S6k/85S6k kinase signalling pathway. Therefore, the minor 4.8-kb mRNA generates a constitutive production of prepro-IGF-II, whereas the major 6.0-kb mRNA provides a post-transcriptionally regulated species.

Anisomycin↗
PubMed1995

Evidence favouring different descending pathways to soleus motoneurones activated by magnetic brain stimulation in man.

1. In resting subjects low-intensity magnetic stimulation of the brain evoked an inhibition of the soleus H reflex at short latency (conditioning-test interval, -2 to +1 ms) followed approximately 10 ms later by a period of facilitation. During voluntary dynamic or tonic plantar flexion the same stimulus evoked a facilitation with a shorter latency than the inhibition (conditioning-test interval, -5 to -1 ms). 2. At the onset of ramp-and-hold plantar flexion the short-latency facilitation was seen at lower intensities of stimulation than the long-latency facilitation in six of seven subjects. At rest and/or during tonic plantar flexion the opposite was observed in four of the subjects, whereas the two facilitations had approximately the same threshold in the remaining subjects. 3. The short-latency facilitation decreased approximately 100 ms after the onset of ramp-and-hold plantar flexion in all of eight subjects. The long-latency facilitation, in contrast, either had the same size throughout the ramp phase or even increased around the end of the ramp phase. 4. The short-latency facilitation of the reflex was significantly larger at the onset of a fast ramp-and-hold plantar flexion (10 N m (150 ms)-1) than at the onset of a slow contraction (10 N m (600 ms)-1), whereas the opposite was the case for the long-latency facilitation. 5. As the short- and long-latency facilitations had different thresholds and were differently regulated during voluntary movement, it is suggested that they are caused by activation of different descending pathways by the magnetic stimulus.

Adult↗
PubMed1995

Changes in the effect of magnetic brain stimulation accompanying voluntary dynamic contraction in man.

1. The soleus (Sol) H reflex was conditioned by magnetic stimulation of the contralateral motor cortex at rest and during voluntary contraction in healthy human subjects. The intensity of the magnetic stimulus was adjusted so as to have no effect on the H reflex at rest. During tonic voluntary contraction the same magnetic stimulus produced a facilitation with a short latency and a long duration, thus reflecting an increased excitation of Sol motoneurones by the magnetic stimulus during voluntary contraction. 2. The amount of reflex facilitation produced by brain stimulation within the initial 0.5-1 ms after its onset was investigated at different times during dynamic ramp-and-hold plantar flexion. The facilitation was largest at the onset of voluntary activity in the Sol muscle. It then decreased abruptly within 100 ms after the onset of the voluntary contraction. Neither the voluntary Sol activity nor the control H reflex decreased at this time. 3. Electrical stimulation of the brain with the anode placed lateral to the vertex produced a facilitation of the H reflex, which preceded the facilitation evoked by magnetic stimulation by 1-2 ms. The facilitation produced by the magnetic stimulus occurred or increased at the onset of contraction in relation to rest in all experiments. However, this was the case in only two out of eight experiments, when the brain was stimulated electrically. 4. The size of the reflex facilitation measured at the onset of contraction was larger the faster the contraction. Positive correlations were found between the size of the facilitation and the peak of the first and second derivative of the torque and the peak Sol EMG activity. 5. It is suggested that the observed changes in the size of the short-latency reflex facilitation produced by magnetic brain stimulation mainly reflects changes in the excitability of corticospinal cells, since similar changes were not observed in the size of the unconditioned Sol H reflex or in the short-latency reflex facilitation produced by electrical brain stimulation. The data support the hypothesis that fast conducting corticospinal fibres with monosynaptic projections to spinal motoneurones are involved in the initiation of voluntary movement in man.

Adult↗
PubMed1995

Latency of effects evoked by electrical and magnetic brain stimulation in lower limb motoneurones in man.

1. The latency of effects in the tibialis anterior (TA) and soleus (Sol) muscles evoked by electrical and magnetic stimulation of the motor cortex was evaluated in human subjects by H reflex testing. Post-stimulus time histograms (PSTHs) were established for the discharge of single voluntarily activated motor units and motor-evoked potentials (MEPs) in the surface electromyogram. 2. At rest both electrical and magnetic stimulation evoked an inhibition of the Sol H reflex at the lowest intensities of stimulation. In some subjects a facilitation with an earlier onset was seen when increasing the stimulation strength. When the anode for the electrical stimulation was placed at the vertex directly above the leg motor area, the inhibition or facilitation often had the same latency as when evoked by magnetic stimulation. However, when the anode was placed 2-3 cm lateral to the vertex, effects evoked by the electrical stimulus often occurred 1-2 ms earlier. 3. Short-latency peaks in the PSTH of the discharges of single TA motor units also tended to occur earlier when evoked by electrical stimulation with the anode lateral to the vertex than when evoked by magnetic stimulation or electrical stimulation with the anode at the vertex. 4. In one subject, near-maximal electrical stimulation evoked MEPs with a latency corresponding to that seen following stimulation of the brainstem by electrodes placed bilaterally over the mastoid processes approximately 16 cm more distal. Maximal magnetic stimulation, in contrast, never resulted in responses with a latency shorter than that seen with the weakest electrical stimuli at the vertex. 5. The initial facilitation of the Sol H reflex evoked by magnetic stimulation and by electrical anodal stimulation at the vertex increased when the subject performed a voluntary plantarflexion. In contrast, the earlier facilitation evoked by electrical anodal stimulation 2-3 cm lateral to the vertex had the same size both at rest and during contraction. 6. We suggest that magnetic stimulation and electrical anodal stimulation at the vertex may preferentially activate descending cortical cells at, or close to, the cell soma. The initial responses evoked by these two stimuli may therefore be influenced by the excitability of the cortical cells. On the other hand, electrical stimulation with the anode 2-3 cm lateral to the vertex seems to often activate the axons at a deeper level. The initial responses evoked by this type of stimulation may therefore not be influenced by the excitability of the cortical cells.

Adult↗
PubMed1995

Regulation of angiotensin II receptor expression in ovarian follicles. A review.

The regulation of angiotensin (Ang) II receptor expression in ovarian follicles was reviewed. Ang II receptor expression, assessed as the Ang II binding capacity, varied with the animal species and the developmental stage of the follicle. In cows, the expression correlated positively with follicular size and negatively with the active renin concentration in the follicular wall tissue. No relations were found to the follicular fluid concentrations of prorenin, estradiol or progesterone. In cell cultures, luteinizing hormone up-regulated Ang II receptor expression in cows, whereas it was decreased by follicle-stimulating hormone, Ang II and testosterone in rats. These data support the concept of an active and regulated RAS in ovarian follicles. The species differences in Ang II expression suggest varying functional roles of the RAS between species.

Angiotensin II↗
PubMed1995

Analysis of penicillin V biosynthesis during fed-batch cultivations with a high-yielding strain of Penicillium chrysogenum.

Metabolites (both intra- and extracellular) involved in penicillin biosynthesis were measured during fed-batch cultivations with a high-yielding strain of Penicillium chrysogenum. The fed-batch cultivations were carried out on a complex medium containing corn steep liquor. Three distinct phases were observed: (a) a rapid growth phase where free amino acids present in the medium are metabolized, (b) a linear growth phase, and (c) a stationary phase. The specific penicillin production (rp) is initially high and, during the rapid growth phase, it increases slightly. During the linear growth phase rp is approximately constant [4-6 mg penicillin V (g dry weight)-1 h-1 depending on the operating conditions], whereas it decreases during the stationary phase. During the cultivations the tripeptide Aad-Cys-Val (the first metabolite in penicillin biosynthesis) and 8-hydroxypenillic acid (formed by carboxylation of 6-aminopenicillanic acid, 6-APA) were found to accumulate in the medium, whereas the concentrations of isopenicillin N and 6-APA were found to be approximately constant and low. About 3% of the Aad-Cys-Val formed in the first step of the penicillin biosynthetic pathway is lost to the medium and 4% of the isopenicillin N formed in the second step of the pathway is lost as extracellular isopenicillin N, 6-APA or 8-hydroxypenillic acid. Also the cyclic form of alpha-aminoadipic acid, 6-oxo-piperidine-2-carboxylic acid, was found to accumulate in the medium and it was found to be formed in an approximately constant ratio to penicillin V of 6 mol/100 mol.

Penicillin V↗
PubMed1995

Central control of reciprocal inhibition during fictive dorsiflexion in man.

The size of the soleus Hoffmann reflex (H-reflex) was measured in six healthy human subjects before and after transmission in the common peroneal nerve (CPN) was blocked reversibly by local injection of lidocaine. It was found that the H-reflex at rest increased after the block. When the subjects attempted to perform a dorsiflexion while the CPN was blocked ("fictive dorsi flexion"), the soleus H-reflex was strongly depressed. Stimulation of the CPN proximal to the block elicited a short-latency inhibition of the soleus H-reflex, which was probably mediated by reciprocal Ia interneurones. This inhibition never increased during dorsiflexion relative to rest prior to the CPN block, but after the block a significant increase in inhibition was seen during fictive dorsiflexion in three subjects. Stimulation of the femoral nerve (FN) elicited a short-latency monosynaptic Ia facilitation of the soleus H-reflex. This facilitation was found to decrease during dorsiflexion relative to rest before the block as well as during fictive dorsiflexion after the block. The decrease in the H-reflex during fictive dorsiflexion demonstrates that although an increased Ia-afferent feedback via the gamma-loop may contribute to reciprocal inhibition when transmission in the CPN is intact, a noticeable, centrally mediated inhibition may occur in the absence of this feedback. It is suggested that this inhibition is caused by central facilitation of interneurones mediating disynaptic Ia inhibition as well as interneurones mediating presynaptic inhibition of Ia afferents.

Adult↗
PubMed1995

Cancer incidence in men with Klinefelter syndrome.

Many case reports have suggested an association between Klinefelter syndrome (KS) and cancer, but studies of the cancer incidence in larger groups of men with KS are lacking. A cohort of 696 men with KS was established from the Danish Cytogenetic Register. Information on the cancer incidence in the cohort was obtained from the Danish Cancer Registry and compared with the expected number calculated from the age, period and site specific cancer rates for Danish men. A total of 39 neoplasms were diagnosed (relative risk = 1.1). Four mediastinal tumours were observed (relative risk = 67); all four were malignant germ cell tumours. No cases of breast cancer or testis cancer were observed. One case of prostate cancer occurred within a previously irradiated field. No excess of leukaemia or lymphoma was found. An increased risk of cancer occurred in the age group 15-30 years (relative risk = 2.7). All six tumours in this group were germ cell tumours or sarcomas. The overall cancer incidence is not increased and no routine cancer screening seems to be justified. A considerably elevated risk of mediastinal germ cell tumours occurs in the period from early adolescence until the age of 30.

Adolescent↗
PubMed1995

Changes in transmission across synapses of Ia afferents in spastic patients.

The transmission across synapses of Ia afferents on spinal motor neurons was investigated in 30 healthy subjects and 25 spastic multiple sclerosis patients. Slow passive stretch (17 degrees/s of the soleus muscle evoked a pronounced depression of the soleus Hoffmann reflex (H-reflex) lasting for more than 10 s in the healthy subjects. This depression was less pronounced and had a shorter duration in the spastic patients. A tap applied to the biceps femoris tendon also produced an inhibition of the soleus H-reflex, which was larger in the healthy subjects than in the spastic patients. This inhibition only lasted for 300-400 ms. Finally, stimulation of the femoral nerve (FN) produced a facilitation of the soleus H-reflex, which was larger in the spastic patients than in the healthy subjects. The inhibition of the H-reflex evoked by the biceps femoris tendon tap is known to be caused by presynaptic inhibition of the Ia afferents, which mediate the reflex. The facilitation of the soleus H-reflex produced by FN stimulation has also been shown to be influenced by changes in presynaptic inhibition. The increased facilitation from the FN and the decreased inhibition from the biceps femoris tendon tap onto the soleus H-reflex in spastic patients are thus both compatible with a deficient presynaptic inhibition in these subjects. The long lasting depression of the reflex evoked by a previous slow stretch of the soleus muscle is most likely caused by a decrease of the probability of transmitter release from the Ia afferents. The decrease of this depression in spastic patients suggests that mechanisms other than presynaptic inhibition may contribute to changes in the efficiency of transmission across the synapses of Ia afferents in spastic patients and thus contribute to the exaggeration of stretch reflexes seen in these patients.

Adult↗
PubMed1995

Induction and repression of alpha-amylase production in batch and continuous cultures of Aspergillus oryzae.

The intra- and extracellular concentrations of alpha-amylase in Aspergillus oryzae have been measured during batch culture of a wild-type strain and two recombinant strains. The mean intracellular level for the two recombinant strains was about four to five times the level of the wild-type strain. The recombinant strains also had a higher alpha-amylase productivity, whereas the residence time of the intracellular alpha-amylase pool was approximately the same for the three strains. At high glucose concentrations there was a low constitutive synthesis of alpha-amylase, whereas at low glucose concentrations derepression resulted in an increased production rate. Shifts from a glucose- to a maltose-limited chemostat showed that maltose induces both the production and secretion of alpha-amylase. Finally, from immunoblots, both a glycosylated and an unglycosylated alpha-amylase have been detected.

Amidohydrolases↗
PubMed1995

Parental origin of the X chromosome, X chromosome mosaicism and screening for "hidden" Y chromosome in 45,X Turner syndrome ascertained cytogenetically.

Our study confirms the finding that about 85% of X chromosomes in Turner girls are maternally derived. A new observation is the detection of a high frequency of mosaicism (15%) in Turner girls who by cytogenetic analysis were thought to have a pure 45,X karyotype. DNA examination of the material was done by hybridization with digoxigenin labelled, non-radioactive probes, and PCR products for microsatellite analysis were run on polyacrylamide gels. We screened for the presence of "hidden" Y chromosome mosaicism, using the primers SRY, ZFY, DYZ3, DYZ1 and DYS132. Contrary to other reports using the PCR technique to unravel "hidden" Y chromosome mosaics, we did not find any positive cases. A precise technical protocol for these new techniques is given, and the advantages are discussed.

Chromosome Banding↗
PubMed1995

Mechanical and electromyographic analysis of reciprocal inhibition at the human ankle joint.

1. The purpose of the present study is to investigate how reciprocal inhibition influences the mechanical and electromyographic (EMG) properties of the ankle plantar flexors in humans during a voluntary contraction. 2. At different levels of maintained plantar flexion contractions ranging from 0 to 20 Nm, the size of the soleus EMG stretch reflex and the ankle joint stiffness (ration between the torque increment and the amplitude of the stretch) were measured in response to an imposed dorsiflexion. At matched plantar flexion contraction levels, stretch responses were compared before and after reversible block of the common peroneal nerve (CPN). Stretch responses were also measured during an attempted voluntary fictive dorsiflexion after CPN block. 3. In the preactivated soleus muscles, the phasic EMG response to stretch consisted of two peaks labeled M1 and M2. After CPN block, the M1 short-latency stretch reflex on average increased by 25 +/- 5.7%, mean +/- SD (P < 0.001), and the M2 stretch reflex increased on average by 29 +/- 13.0% (P = 0.002). 4. The total stiffness of the ankle joint during a stretch is the sum of the nonreflex and the reflex mediated stiffness. The total stiffness after CPN block increased on average by 13 +/- 2.7% (P = 0.002) and the estimated reflex stiffness by 33 +/- 6.5% (P < 0.001). 5. When the subjects were asked to make a strong dorsiflexion after CPN block, the soleus stretch reflex was depressed to the extent that the reflex mediated mechanical effect around the ankle joint was abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates.

The synthesis of a series of alkylcarbamates of 1,5-methano-2,3,4,5-tetrahydro-1H-2-benzazepin-7-ol is reported. Many of these compounds are potent acetylcholinesterase (AChE) inhibitors. The in vitro AChE inhibition, cholinergic effects, acute toxicity, and elevation of brain acetylcholine levels in vivo of this series of compounds are described. A representative compound, 1d (5.6 mg/kg, po), was able to reverse hemicolinium-3-induced amnesia in the mouse passive avoidance assay.

Administration, Oral↗
PubMed1994

Is presynaptic inhibition distributed to corticospinal fibres in man?

1. A tendon tap of the biceps femoris tendon was found to evoke a depression of the soleus and tibialis anterior H reflexes with a duration of 300-400 ms and with an onset at a conditioning-test interval of 20-30 ms. It is suggested that the depression is caused by presynaptic inhibition of the terminals of the Ia afferents mediating the reflexes. 2. This possibility was tested by a method in which the H reflex is facilitated by a monosynaptic Ia volley from the quadriceps muscle. The attenuation of this facilitation when another pathway is stimulated is probably caused by presynaptic inhibition of Ia afferents. It was shown that the biceps femoris tendon tap depressed the size of the femoral nerve-induced facilitation of the soleus and tibialis anterior H reflexes. This suggests that the depression of the reflexes by the tendon tap was indeed caused by presynaptic inhibition. 3. To investigate whether the terminals of descending fibres were similarly susceptible to presynaptic inhibition, the stimulation of the femoral nerve was replaced by magnetic stimulation of the contralateral motor cortex. This stimulation has been shown to evoke a facilitation of the tibialis anterior and soleus H reflexes which (within its initial 0.5-1 ms) is probably caused exclusively by direct monosynaptic projections from the cortex to the motoneurones. In contrast to the facilitation evoked by Ia afferents, the descending facilitation was not influenced by the biceps tendon tap. 4. Similarly, the monosynaptic peak in the post-stimulus time histogram (PSTH) of single voluntarily activated tibialis anterior motor units evoked by stimulation of the common peroneal nerve was depressed by the tendon tap, whereas this was not the case for the presumed monosynaptic peak evoked by brain stimulation. 5. It is suggested that the tendon tap evoked presynaptic inhibition of the terminals of flexor as well as extensor Ia afferents terminating on both soleus and tibialis anterior motoneurones. In contrast, the tap failed to elicit any presynaptic inhibition of the terminals of descending fibres on the motoneurones. We suggest that descending pathways in general are free from the presynaptic control which attenuates peripheral input to motoneurones. Through modulation of presynaptic inhibition the brain may thus selectively hinder the access of peripheral feedback mechanisms to the motoneurones, while still maintaining control of the output from the spinal cord through direct and indirect projections to the motoneurones.

Adult↗
PubMed1994

Discharge of muscle afferents during voluntary co-contraction of antagonistic ankle muscles in man.

The discharge of 38 tibialis anterior (TA) muscle spindle endings was recorded at rest and during isometric voluntary contraction of the ankle joint in eight healthy human subjects. With the ankle joint in 110 degrees plantarflexion, 24 endings (61%) were tonically active in the resting subject. During weak voluntary dorsiflexion, seven additional endings were activated, so that a total of 31 endings were active (82%). 24 of these were either newly recruited or discharged at a faster rate than at rest (average discharge rate 6.6 Hz at rest, 9.7 Hz during contraction). At matched levels of TA EMG, one ending was newly recruited and 10 were more active during co-contraction of dorsi and plantar flexors than during isolated dorsiflexion. 26 endings were equally active during the two tasks and one ending decreased its firing rate with co-contraction. Four of the 11 endings, which had a higher discharge rate during co-contraction than during dorsiflexion, discharged faster during plantarflexion than at rest although slower than during co-contraction. Plantarflexion had no effect on the discharge of three endings. The remaining four endings were not investigated during plantarflexion. It is suggested that the increased discharge rate of muscle endings during co-contraction is caused either by small changes in the length of the TA muscle or by a disproportionately high fusimotor drive during co-contraction.

Ankle↗
PubMed1994

Segmental reflexes and ankle joint stiffness during co-contraction of antagonistic ankle muscles in man.

The size of soleus H-reflexes and short-latency stretch reflexes was measured at different levels of plantar flexion or co-contraction (simultaneous activation of dorsi- and plantar flexors) in seven healthy subjects. In four of seven subjects the short-latency stretch reflex was smaller during weak co-contraction than during isolated plantar flexion at matched background electromyogram (EMG) levels in the soleus muscle. In three of these four subjects the stretch reflex was larger during strong co-contraction than during plantar flexion, whereas it had the same size during the two tasks in the last subject. In the remaining subjects the stretch reflex either had the same size or was larger at all levels of co-contraction than at similar levels of plantar flexion. In contrast, the H-reflex was found to decrease with co-contraction at all contraction levels in all subjects. The decrease in the reflexes during weak co-contraction might be caused by presynaptic inhibition of Ia afferents. It is unclear why only the H-reflex decreased during strong co-contraction. The stiffness of the ankle joint was measured from the torque increment following the stretch of the plantar flexors divided by the stretch amplitude. In all subjects the total stiffness of the ankle joint was larger during strong co-contraction than during plantar flexion of similar strength. The stiffness was smaller during weak co-contraction than during weak plantar flexion in three out of seven subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Synchronization of human leg motor units during co-contraction in man.

Cross-correlograms were constructed from the spike trains of pairs of individual motor units recorded from the tibialis anterior (TA) and soleus (Sol) muscles. In most correlograms the synchronization consisted of a central peak with a short duration. When the motor units were recorded from the same muscle this synchronization was seen in almost 100% of the cases (TA 92%, Sol 89%) and the peak of synchronization was large (TA 0.060 extra sample spikes per trigger spike, Sol 0.030). In contrast, clear peaks of short duration synchronization was seen in only 4 out of 30 antagonistic TA and Sol motor unit pairs (0.025 extra sample spikes per trigger spike). In another 4 motor unit pairs central troughs were seen. In approximately 10% of all combinations of motor unit pairs a low-amplitude long-duration synchronization was seen. This type of synchronization was seen either as the only type of synchronization or at the same time as the short-duration synchronization. Finally, secondary peaks on both sides of the central peak were seen in a few cases. The distance between the sites of recording of TA motor unit pairs was systematically varied. The latency of the short-duration synchronization became longer and the amount of synchronization smaller the longer the distance between the recording sites. The amount of synchronization of two motor units recorded from the same muscle was shown to be larger when the muscle was activated in co-contraction rather than in an isolated agonist movement. The results are discussed in relation to the organization of the descending command eliciting co-contraction.

Electromyography↗