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Biomedical subjects

B Conrad

Publications and source records attributed to B Conrad.

At least 109 records · Page 6Linked to original sources

Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology.

Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease whose onset is believed to be triggered by unknown environmental factors acting on a predisposing genetic background. Islet-infiltrating T (IIT) cells from two IDDM patients, who had died at the onset of the disease from brain swelling as a complication of ketoacidosis, were analysed. The results provided evidence for the involvement of a pancreatic islet cell membrane-bound superantigen as a diabetes aetiopathogenetic factor. There was a selective expansion of a T-cell receptor (TCR) variable segment of the beta-chain (V beta 7) in these IIT cells in association with unselected V alpha-chain segments; extensive junctional diversity of the TCR V beta 7 chains; and evidence of positive selection, after exposure to diabetic islet cell membrane preparations, of V beta 7+ T-cell clones among peripheral blood lymphocytes from non-diabetic individuals.

Amino Acid Sequence↗

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↗

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↗

A longitudinal model of maternal self-efficacy, depression, and difficult temperament during toddlerhood.

The purpose of this study was to test a model of maternal self-efficacy during toddlerhood using a longitudinal sequential design. Participants were 126 mothers of 1-year olds (Cohort 1) and 126 mothers of 2-year olds (Cohort 2) who completed questionnaires measuring maternal self-efficacy, depression, and perceived difficult toddler temperament three times over 1 year. Data were analyzed using structural equation modeling and maximum likelihood estimation. Findings support a model whereby (a) the more depressed the mother feels, the more likely she is to rate her toddler's temperament as difficult, (b) the more difficult the child's temperament is perceived to be, the lower the mother's estimates of her parenting self-efficacy, (c) the lower the mother's self-efficacy, the greater her depression, and (d) the more depressed the mother feels at one point in time, the more likely she is to remain depressed 6 months later. Implications of the findings are discussed as they relate to self-efficacy theory and nursing intervention with parents of difficult toddlers.

Adult↗

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↗

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↗

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↗

[The importance of 24-hour-blood pressure monitoring in hemodynamic and thromboembolism-induced cerebral infarcts].

Night and day blood pressure profiles of 45 patients with cerebral infarction of hemodynamic or thromboembolic origin were assessed to detect subsequent changes of circadian blood pressure variability. The data were also analysed for a possible relationship between variability of circadian blood pressure, site of cerebral infarction and activation of the autonomic nervous system. Patients with a stroke of hemodynamic origin, when compared to a control group, manifested significantly greater variability of circadian blood pressure (diastolic: -25.2 +/- 4.5% vs. -13.8 +/- 6.5%; p < 0.005). Patients who showed the greatest decrease in vasomotor reactivity (< 40%) developed a prolonged disturbance of the blood-brain barrier. This disturbance regressed slowly only after the pathological 24-hour blood pressure profile had normalized. By way of contrast, patients with cerebral infarctions due to thromboembolic events, when compared to normal individuals, showed a distinctly decreased circadian blood pressure variability (diastolic: -5.2 +/- 6.9%). Initially 40% of these patients presented a pathological increase of nocturnal blood pressure. Circadian blood pressure variability was positively correlated with serum concentration of norepinephrine (r = 0.79; p < 0.01). Patients with a stroke affecting the insular cortex manifested an increase of nocturnal blood pressure significantly more often (66.7% vs. 11.8%; p < 0.005), indicating increased sympathetic activation. They had higher serum levels of norepinephrine (540 +/- 110 pg/ml vs. 290 +/- 178 pg/ml) as compared to patients without damage to the insula and also a significantly higher incidence of prolonged QT intervals and cardiac arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Increased striatal glucose consumption in Sydenham's chorea.

Positron emission tomography and 18F-fluorodeoxyglucose were used to measure the regional cerebral glucose consumption in a 15-year-old choreatic girl with classical Sydenham's chorea shortly after the onset of hyperkinetic movements and 5 months later after chorea had resolved and in a 74-year-old hemichoreatic woman with long-standing hyperkinesia as a residuum of Sydenham's chorea in adolescence. Whereas cerebellar, thalamic, and cortical glucose consumption was within normal limits in both patients, lentiform and caudate glucose consumption was significantly increased in both hemispheres of the 15-year-old patient and in the hemisphere contralateral to the chorea in the 74-year-old patient. In the younger patient, striatal glucose consumption returned to normal after her hyperkinesia had disappeared with antibiotic therapy. The observation of an increase in striatal glucose consumption in Sydenham's chorea, in contrast to the decrease of this variable encountered in the vast majority of other choreatic disorders, leads to questioning the pathophysiology of chorea in humans and suggests the use of emission tomographic measurement of variables related to cerebral energy metabolism for differential diagnosis in choreatic disorders.

Adolescent↗

The value of magnetic stimulation in the diagnosis of radiculopathies.

We studied 42 patients with cervical and lumbar radiculopathies using magnetic stimulation. Prolonged latencies following magnetic stimulation of the brain, the paravertebral spinal nerve, or both, showed a highly significant correlation with muscle weakness in clinical testing (24 of 26 patients with weakness had pathological motor evoked potentials) as well as with spontaneous activity of the target muscles in needle electromyography (24 of 25 subjects). The determination of both the central and the peripheral motor conduction time was found to be essential in patients with radiculopathies, because different patterns of latency changes correlated with different morphological results in computed tomography: in patients diagnosed as having a lateral compression of the nerve root the peripheral nerve latency was delayed; whereas, in patients with more medially localized herniations, a prolonged central motor latency was the most frequent finding. This study posits that combined magnetic stimulation of the brain and nerve root is an effective and painless technique for the noninvasive evaluation of nerve root function.

Adult↗

PC-based system for an objective quantification of manual movement disability for clinical and scientific purposes.

In clinical management and research of movement disorders exact knowledge about the extent of motor impairment is essential. This paper presents a computer program which allows for an objective measurement of manual movement disability. The program was developed for standard hardware and can easily be used in a variety of clinical and research environments. The program runs on MS-DOS computers and uses a Microsoft computer mouse as the only input device. The temporal resolution is 100 Hz, the spatial resolution 400 dots per inch. The user may choose between standard test sets or he may design sets according to his individual needs from a pool of available protocols which includes tracking tasks, ballistic tasks, complex sequential tasks, and finger tapping. All tasks are implemented in a similar way in order to keep the test environment as consistent as possible for the patient. The patient must usually carry out movements which correspond to the movements of a target symbol on the computer screen. This entails the manipulation of a follower symbol, also visible on the computer screen, via the computer mouse. The program itself and the theoretical background of the protocols are described in the paper. Additionally, preliminary results from pilot experiments are presented.

Computer Simulation↗

Designing interventions in psychosocial research.

There is little guidance in the literature on how to design cost-effective interventions for preventing or treating psychosocial health care problems. Four sources of information are described for developing interventions that are based on a strong theoretical and empirical foundation: (1) an explicit theory for intervention, (2) supporting descriptive data, (3) an evaluation of possible intervention strategies that are consistent with the theory and the supporting data, and (4) focus groups to examine the feasibility and external validity of the intervention before formal testing.

Child Behavior Disorders↗

Evidence for early Th 2 T cell predominance in xenoreactivity.

Two distinct subsets of CD4+ Th lymphocytes have been characterized by their cytokine profiles: Th 1 (TH1) and Th 2 (TH2). While TH1 cells predominate in cell-mediated responses, TH2 cells support the humoral response. We have examined the mRNA cytokine profile of normal mouse lymphocytes in response to alloantigen versus xenoantigen (rat) in MLC, and present evidence to suggest that early in proliferative responses, alloreactivity is dominated primarily by TH1-type lymphocytes, while xenoreactivity is predominantly TH2. Normal mouse lymphocyte-responding cells were cultured in a one-way MLR with either allo or xeno antigen and examined for production of mRNA for cytokines characteristically produced by TH1 (IL-2, IFN-gamma) or TH2 (IL-4, IL-10) cells. Semiquantitative reverse transcription-polymerase chain reaction analysis was performed for mouse IL-2, IL-4, IL-10, and IFN-gamma mRNA. In the mouse anti-rat xeno response, mRNA for TH2 gene products were upregulated, with greater levels of IL-4 and IL-10 at 24 and 48 hr when compared with controls. In contrast, upregulation of mRNA for TH1 gene products occurred in the mouse anti-mouse allo response, with higher levels of IL-2 and IFN-gamma at 24 and 48 hr. In the anti-xeno response, upregulation of all 4 cytokines occurred by day 4 and peak levels of mRNA for all cytokines examined were 2-3 times that seen for the peak anti-allogeneic response. These data suggest that early xenorecognition may differ from allorecognition by differential activation of the TH2 subset. A better understanding of the balance between Th subset function and cytokine profile in allo and xeno reactivity may allow a more targeted and specific approach to control the early events in xenograft rejection.

Animals↗

Determination of nerve growth factor concentrations in human samples by two-site immunoenzymometric assay and bioassay.

Nerve growth factor is a neurotrophic protein which is known to act on sympathetic and sensory neurons and on the magnocellular cholinergic neurons of the basal forebrain. We quantified nerve growth factor in human tissue and body fluids by two methods, a rapid and sensitive two-site immunoenzymometric assay and a bioassay using dissociated chick dorsal root ganglion neurons. The two-site immunoenzymometric assay detects nerve growth factor in concentrations as low as 0.5-2.5 ng/l. Using a monoclonal antibody to mouse nerve growth factor, we found that the signal of the antibody for recombinant human nerve growth factor is about 60-90% of the signal for mouse nerve growth factor. As a control for the specificity of our data, a bioassay for nerve growth factor was performed and the results showed a good correlation. The highest nerve growth factor concentrations were found in sciatic nerve (2.5 ng/g wet weight), cardiac atrium muscle (1.5 ng/g wet weight) and in the central nervous system in the hippocampus (1.9 ng/g wet weight). Lower nerve growth factor concentrations were measured in human sera (0.2 ng/g wet weight). No nerve growth factor was detectable in cerebrospinal fluid. The distribution of human nerve growth factor-rich tissues is similar to that reported for rat tissues.

Animals↗