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Biomedical subjects

B Conrad

Publications and source records attributed to B Conrad.

At least 19 recordsLinked to original sources
PubMed1995

Hybrid Bacillus amyloliquefaciens X Bacillus licheniformis alpha-amylases. Construction, properties and sequence determinants.

A series of 33 single and mosaic hybrid alpha-amylases was constructed from the genes amyBA or amyLI, encoding the alpha-amylases from Bacillus amyloliquefaciens (AmyBA) and Bacillus licheniformis (AmyLI). The hybrid proteins, consisting of the entire alpha-amylase sequence with a variable portion of AmyBA or AmyLI origin, were characterized in order to find enzymes with new properties (thermostability, temperature and pH optima, and substrate specificity), and to localize the amino acid sequence regions responsible for the changes. The thermostability of the AmyBA/AmyLI (AL-type) hybrid proteins correlated with the position and the length of the hybrid sequence. The hybrid enzymes fell into six groups retaining, in comparison to AmyBA, a certain value of the extra-thermostability of AmyLI or becoming more thermolabile than AmyBA. Four regions are proposed to contain thermostability determinants (TSDs). They map between amino acid residues 34-76, 112-142, 174-179 and 263-276 of the respective hybrid enzymes, indicating the dominance of the N-terminal half of AmyLI for these hybrid enzymes' resistance against irreversible inactivation. Two (TSD3 and TSD4) coincide with regions I and II that had already been suggested to stabilise AmyLI [Suzuki, Y., Ito, N., Yuuki, T., Yamagata, H. & Udake, S. (1989) J. Biol. Chem. 264, 18,933-18,938]. The temperature dependence of activity of the AL-type hybrid alpha-amylases was compared at pH 6.4 and pH 7.6 and the hybrid enzymes of one thermostability group were found to have similar temperature responses. A hybrid region between residues 34-76 is demonstrated to correlate with the alpha-amylases' substrate specificity, i.e. either hydrolysis or accumulation of maltohexaose. This region was therefore named the G6G5 region. The exchange of internal sequences between residues 17-201 of AmyBA by the AmyLI counterpart in ALA-type mosaic hybrid alpha-amylases, with one exception (ALA99-429), unexpectedly destabilized the respective ALA-type hybrids. Two of these hybrid alpha-amylases (ALA17-151 and ALA76-151) were less thermostable than AmyBA, while others (ALA112-151, ALA112-201) were enzymically inactive. These data support specific roles of the predicted A1-B domain portion between residues 17-201 of those Bacillus alpha-amylases probably for correct folding and enzymic activity.

Amino Acid Sequence↗
PubMed1995

Influence of baclofen upon the alpha-motoneuron in spasticity by means of F-wave analysis.

Intrathecal baclofen dramatically improves severe spastic syndromes. This improvement is likely related to reduced excitability of alpha-motoneurons. To investigate the influence of baclofen upon the alpha-motoneuron, we analyzed F-waves before and after intrathecal baclofen bolus injection (usually 50 micrograms) as well as after administration of different, constantly delivered doses (60-200 micrograms/day). Intrathecal baclofen bolus decreased the maximum F-wave amplitude (Fp) from an initial value of 9% of the maximum M amplitude (Mmax) (= F/M-ratio) to 2.4% of the Mmax after 130-180 min, reduced the mean F-wave amplitude 60% within 150 min, and shortened the mean duration by 40-60% after 130-180 min. Constantly delivered baclofen of 100 micrograms/day reduced the F/M-ratio from 5% to 2%, the mean F-wave amplitude by 40-80%, and the F-wave mean duration by 40-80%. The minimum F-wave latency did not change after bolus or during steady state administration. The findings indicate that the F-wave mean and maximum amplitude as well as the mean duration are altered in a quantifiable manner following intrathecal baclofen application.

Baclofen↗
PubMed1995

Dynamics of cerebral blood flow velocities during normal human sleep.

Bilateral flow patterns of the middle cerebral artery (MCA) were recorded continuously throughout the night in 18 healthy male subjects (mean age 27.4 years) by a computer-assisted pulsed Doppler (2 MHz) system together with simultaneous polysomnography. After inception of sleep, mean flow velocity (MFV) decreased steadily during deepening sleep stages reaching -15.0 +/- 3.6% (p < 0.001) in the right MCA and -16.2 +/- 3.4% in the left MCA (p < 0.001) in stage 4 of the first sleep cycle compared to the waking state. Lowest MFV values were found in stage 2 preceding the last REM period (right MCA: -19.2 +/- 4.1%: left MCA: -19.7 +/- 5.1%). Changing from non-REM into REM sleep, a sudden rise of MFV, which varied from 8.9% (first sleep cycle, left MCA) to 18% (last sleep cycle, right MCA), could be consistently detected indicating a coupling of cerebral electrical activity and cerebral perfusion in REM sleep. During non-REM sleep this concomitant change of MFV and EEG activity was only found in the first sleep cycle, whereas no parallel changes could be observed in later sleep cycles. These results indicate a decoupling of EEG measured cerebral electrical activity and perfusion and suggest that factors other than metabolic mechanisms contribute to the regulation of cerebral perfusion during human non-REM sleep.

Adult↗
PubMed1995

Temperament in toddlerhood.

The purpose of this article is to describe how toddler temperament can affect parent-child relations using a goodness-of-fit framework. Nursing considerations for assessing toddler temperament with families and providing parental guidance for managing toddlers with difficult temperament styles are discussed. Emphasis is placed on helping parents to understand their toddler's temperament-based behavior and to devise strategies that maximize compatibility between the toddler's temperament and parental expectations.

Child, Preschool↗
PubMed1995

[Rockwood capsulorrhaphy in shoulder instability. A clinical follow-up study].

Rockwood described a capsulorrhaphy technique for operative treatment of multidirectional shoulder instability with anterior dislocation. We have used this technique mainly in patients with severe multidirectional instability and now have 8 years' experience with it, which is reported below. The surgical technique involves refixation of the Bankart lesion with transosseous suture and double breasting of the anterior capsule. No transposition of the subcapularis muscle was performed. A functional rehabilitation program without immobilization was used in all patients. The daily activity level, the degree of discomfort upon shoulder-related activities and the subjective assessment of outcome were recorded for each patient. General outcome was determined with reference to Rowe's score. A clinical examination was performed as well as radiography. Strength was evaluated by standardized bilateral dynamometry. Follow-up examination was possible in 73 out of 82 patients. The mean age at follow up was 32.7 +/- 4.1 years, and the mean follow-up time, 4.3 years. The reason for surgery was recurrent dislocation in 81% of patients, pain in 4% and both pain and dislocation in 15% of patients. In 8 patients (10.9%) multiple (up to 4) previous surgical attempts by various methods had been unsuccessful. Postoperatively 59% (n = 44) were able to take part in sports without restrictions, 27.4% could take part only in sports not involving the shoulder, and 13.5% (n = 10) did not engage in any sports postoperatively. The redislocation rate was 12.3% (n = 9), and there was 1 traumatic redislocation. A deficit in abduction/elevation by 10-60 degrees was found in 4 patients (5.4%) and by > 60 degrees in 2 patients (2.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Magnetically induced muscle contraction is caused by motor nerve stimulation and not by direct muscle activation.

When magnetically stimulating peripheral nerves, a local cocontraction of muscle under the coil is observed. We assessed whether this contraction results from: (1) magnetic stimulation of motor nerves, or (2) direct depolarization of the muscle membrane. Wrist extensor muscles of normal subjects were magnetically stimulated with the coil placed directly above the muscle. Neuromuscular transmission was then blocked by atracurium using a technique of local curarization. As a reference, the radial nerve was stimulated electrically. Magnetic and electrical stimuli were applied alternatingly every 10 s. Twitch force of wrist extension was measured isometrically over a period of about 70 min including the phase of complete neuromuscular block. Twitch amplitudes elicited by magnetic and electrical stimuli were equivalent during the whole experiment. These results suggest that muscle cocontraction following magnetic stimulation results from depolarization of terminal motor nerve branches.

Action Potentials↗
PubMed1994

Dysfunctional activation of subcortical nuclei in palatal myoclonus detected by high-resolution MRI.

Magnetic resonance images that were sensitized to changes in cerebral blood oxygenation state demonstrated dysfunctional activation of the dentate nuclei, the left inferior olivary nucleus and the left red nucleus in a 56-year-old patient with palatal myoclonus. These findings represent the first demonstration of movement-related activation of cerebellar, brainstem and midbrain nuclei in a single subject and at a spatial resolution comparable to that of anatomic MR images.

Brain Stem↗
PubMed1994

Kinematic properties of slow arm movements in Parkinson's disease.

Present pathophysiological concepts of bradykinesia stress an impairment of fast movements in Parkinson's disease. It is, however, unknown whether "bradykinetic" movements are different from slow movements of normal subjects. We recorded trajectories of unrestrained "natural" arm movements from normal subjects and patients with Parkinson's disease. The experiment required the execution of pointing movements for different movement distances and velocities. The shape of trajectories was found to be changed in Parkinson's disease. The steepness of the initial segment and the relation between steepness of the initial segment and final segment both exceeded corresponding values in normal subjects. An analysis of velocity profiles showed an impaired synchrony of vertical and horizontal velocity components. The difference from normal subjects increased with movement velocity. Parkinsonian patients suffered from a fundamental defect in the composition of complex sequences of motor programs required to perform natural arm movements.

Aged↗
PubMed1994

Repetitive magnetic nerve stimulation: technical considerations and clinical use in the assessment of neuromuscular transmission.

We assessed to what extent repetitive magnetic stimulation can replace the electrical method. Fifteen healthy subjects and 3 patients with myasthenia gravis were investigated using stimulation of the median, ulnar, axillary and accessory nerves. Single, as well as 3/sec repetitive magnetic and electrical stimuli were applied. When comparing the results of magnetic vs. electrical stimulation, amplitudes, areas and shapes of compound muscle action potentials were not significantly different. Although single magnetic stimuli were much less uncomfortable than the electrical stimuli, differences in comfort were much smaller in the repetitive protocol, because muscular contractions under the magnetic stimulation coil caused unpleasant movements of, for example, the neck. Additional problems arose from technical limitations of the prototype magnetic stimulator used: stimulation intensity was significantly limited, resulting in an inability to elicit supramaximal responses in 11 of the 154 investigations. Overheating of the stimulator coil forced us to give the coil extra time to cool down. These problems might be solved in the future by more focused stimulus geometry and introduction of cooling devices. It is concluded that magnetic stimulation can elicit responses which are equivalent to the electrical method in repetitive nerve stimulation. At present due to some shortcomings it cannot replace electrical stimulation in routine repetitive nerve stimulation.

Adult↗
PubMed1994

Relationship between cerebral blood flow velocities and cerebral electrical activity in sleep.

The dynamics of cerebral blood flow velocity during sleep were measured in the right and left middle cerebral artery of 12 and 10 healthy male volunteers, respectively. A computer-assisted pulsed (2-MHz) Doppler ultrasonography system was modified for continuous long-term and on-line recording of cerebral hemodynamics in combination with polysomnography. Mean flow velocity (MFV) decreased steadily during deepening nonrapid eye movement (NREM) sleep and increased suddenly during rapid eye movement sleep, corresponding to changes in brain function. However, spontaneous or provoked changes in sleep stage patterns as well as awakenings from NREM sleep were not regularly accompanied by corresponding changes in MFV. Differing values for MFV in subsequent sleep cycles could be shown for several sleep stages. Furthermore, MFV values in sleep stage II at the end of an NREM-sleep period were lower than in preceding slow-wave sleep. After application of short acoustic signals the electroencephalogram frequency rose, indicating an arousal, whereas MFV rapidly decreased for several seconds and then gradually returned to the prior level. These results imply an uncoupling between cerebral electrical activity and cerebral perfusion during sleep and support a dissociation in the activity of central regulatory mechanisms. In light of the proposal that cortical energy consumption can be accounted for by cerebral electrical activity, the concept that cerebral perfusion during sleep is regulated solely by the metabolic rate must be reconsidered.

Adult↗
PubMed1992

Motor responses evoked by magnetic brain stimulation in psychogenic limb weakness: diagnostic value and limitations.

The latencies and amplitudes of responses evoked by magnetic brain stimulation (magnetic evoked potentials, MEP) in the first dorsal interosseus and the anterior tibial (TA) muscles were investigated in 15 patients with psychogenic limb weakness and in 50 patients with limb weakness due to established organic central nervous system disease. Of the patients with psychogenic limb weakness, 3 presented with upper limb monopareses, 2 with lower limb monoparesis, 4 with hemipareses, 4 with parapareses and 2 with paraparesis. All patients with psychogenic weakness had MEP in arm and leg muscles with latencies within the normal range. MEP amplitudes were also normal except for 1 patient in whom the response amplitude in the TA of the plegic limb was reduced. In patients with limb weakness due to established organic disease, MEP were frequently but not invariably abnormal. In patients with plegic (i.e. completely paretic, MRC grade 0) muscles due to organic disease, MEP always were clearly abnormal. Normal MEP were sometimes elicited from paretic muscles, more commonly in association with cerebral hemisphere lesions than with spinal lesions. We conclude that psychogenic limb weakness is associated with normal MEP. However, normal MEP in mildly paretic muscles do not definitely exclude organic pathology.

Adolescent↗
PubMed1992

Motor responses evoked by magnetic brain stimulation in Huntington's disease.

In 34 patients with manifest Huntington's disease (HD), and in 21 first-degree offspring without clinical signs or symptoms, the sizes, central motor latencies (CMLs) and variation in latencies of EMG responses (MEPs) following transcranial magnetic brain stimulation were studied in muscles of the upper and lower extremities. In subgroups of patients and their offspring median and tibial nerve somatosensory evoked potentials (SEPs) and electrically elicited long-loop reflexes (LLRs) in hand muscles were also investigated. Increased MEP thresholds were observed in 10% of the HD offspring, while CML, latency variability and MEP amplitudes always lay within normal range. In contrast, SEPs were abnormal in 33%. In HD patients MEPs were found to be abnormal in up to 72% of patients when all available response parameters were taken into consideration. MEP abnormalities correlated with the duration of motor symptoms and the severity of choreic motor activity. When both MEPs and SEPs were evaluated, abnormalities could be detected in 91% of all HD patients. We suggest that abnormal MEPs might reflect an altered excitability of the cortico-spinal system as a consequence of basal ganglia dysfunction, rather than a structural damage of the investigated descending pathways. To localize the pathological mechanism responsible for altered LLRs, a "loop analysis" was performed by recording LLRs, MEPs and SEPs in the same patients. Alterations of LLRs correlated best with abnormal SEPs and might therefore be explained by reduced somatosensory input to the motor cortex.

Adolescent↗
PubMed1992

Imprecise excision of plasmid pE194 from the chromosomes of Bacillus subtilis pE194 insertion strains.

Plasmid pE194 has been shown to be rescued by integration after cultivation of infected Bacillus subtilis recE4 cells at a restrictive high temperature. The plasmid is also spontaneously excised from the chromosome at a low frequency by precise or imprecise excision (J. Hofemeister, M. Israeli-Reches, and D. Dubnau, Mol. Gen. Genet. 189:58-68, 1983). We have investigated nine excision plasmids, carrying insert DNA 1 to 6 kbp in length, either in a complete pE194 or in a partially deleted pE194 copy. Type 1 (additive) excision plasmids have the left- and right-junction DNAs preserved as 13-bp direct repeats (5'-GGGGAGAAAACAT-3') corresponding to the region between positions 864 and 876 in pE194. In type 2 (substitutive) excision plasmids, a conserved 13-bp sequence remains only at the right junction while the left junction has been deleted during the excision process. The type 3 excision plasmid carries at each junction the tetranucleotide 5'-TCCC-3', present in pE194 between positions 1995 and 1998. Although we isolated the excision plasmids from different integration mutants, the insert DNAs of eight independently isolated plasmids showed striking sequence homology, suggesting that they originated from one distinct region of the B. subtilis chromosome. Thus, we postulate that imprecise excision of pE194 occurs most frequently after its translocation from the original insertion site into a preferred excision site within the host chromosome. The imprecise excision from this site occurs at excision breakpoints outside the pE194-chromosome junctions in a chromosomal region which remains to be investigated further.

Bacillus subtilis↗
PubMed1992

Assessment of intracranial hemodynamics in sleep apnea syndrome.

BACKGROUND AND PURPOSE: Sleep apnea syndrome may lead to changes in cerebral hemodynamics due to altered alveolar ventilation. We investigated the dynamics of CO2- and blood pressure-regulated alterations of cerebral blood flow velocities during apneic episodes and evaluated CO2 reactivity during different sleep stages. METHODS: A computer-assisted pulsed Doppler system (2 MHz) was used for continuous overnight recordings of middle cerebral artery flow patterns together with simultaneous polysomnography, continuous blood pressure recordings, and measurements of end-expiratory CO2 in six patients with sleep apnea syndrome. RESULTS: Increases in mean flow velocity of 19-219% and in blood pressure of 12.5-83.1% could be observed during the apneic episodes, with maximum increases during rapid eye movement (REM) sleep. CO2 reactivity was in the normal range (4.4 +/- 1.2%) in the waking state and was markedly increased during sleep stages 1 and 2 (p less than 0.005 compared with awake). The greatest increase was found during REM sleep, with a rise of up to three times the waking value (p less than 0.0001 compared with sleep stage 2). CONCLUSIONS: The changes of mean flow velocity could be interpreted as reactive adaptation processes because of CO2 and blood pressure increases corresponding to apnea. The increased CO2 reactivity during sleep may indicate a "hypersensitivity" of intracranial vascular CO2 or pH receptors and a disturbance of central catecholaminergic and cholinergic systems. The pronounced velocity changes during apneic episodes and the concomitant alterations of vessel wall tension might lead to microangiopathies and macroangiopathies due to chronic strain on the brain vessels.

Adult↗