Intrathecal baclofen increases corticospinal output to hand muscles in multiple sclerosis.
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Adult↗
Biomedical subjects
B Conrad
Publications and source records attributed to B Conrad.
Abnormal increase in the corticomotor output to the affected hand during repetitive transcranial magnetic stimulation of the primary motor cortex in patients with writer's cramp.
In fourteen right-handed patients with writer's cramp and 10 right-handed controls, 10 trains of suprathreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) were applied over the left primary motor hand area. Each rTMS train lasted for a minute with an intertrain interval of 10 s. The motor evoked potentials (MEPs) were recorded from the relaxed contralateral first dorsal interosseus muscle. The mean MEP area of each rTMS train was taken as a measure of the corticospinal motor output to the affected hand. While the mean MEP area decreased significantly in controls, patients showed a significant increase in mean MEP area during rTMS. The differential effect on MEP size was highly significant. The abnormal rTMS-associated facilitation of the corticomotor output to the affected hand demonstrates an increased excitability of the corticospinal motor system in writer's cramp.
Adult↗
Repetitive transcranial magnetic stimulation has a beneficial effect on bradykinesia in Parkinson's disease.
The effect of focal 5 Hz repetitive transcranial magnetic stimulation (rTMS) of the motor hand area (M1) on bradykinesia was studied in 12 unmedicated patients with Parkinson's disease (PD). On 2 separate days, a real-rTMS was applied to M1 contralaterally to the more severely affected limb or a frontal sham-rTMS was applied 3 cm anteriorly to Fz in a random order. Stimulus intensity was 10% below resting motor threshold. Before and 20 min after rTMS, patients performed 15 consecutive pointing movements with the index finger contralaterally to the stimulated M1. Compared with sham-rTMS, real-rTMS over the contralateral M1 caused a significant decrease in total movement time without affecting end-point accuracy. Our data provide evidence that 5 Hz rTMS over M1 can improve bradykinesia in PD patients beyond the time of magnetic stimulation.
Adult↗
Multiple A waves in Guillain-Barré syndrome.
In 13 of 14 patients with Guillain-Barré syndrome (GBS), we observed multiple A waves in at least one limb nerve on routine electroneurographic studies within 7 days after onset of symptoms. The patient without A waves had a severe axonal type of GBS with tetraplegia and almost complete loss of M responses following electrical stimulation of limb nerves. In the remaining 13 patients, on average 8 +/- 2 (mean +/- SD) A waves were present in each tibial nerve (n = 24) and 4 +/- 1 A waves in each peroneal nerve (n = 26). About half of the A waves were below 50 microV in amplitude, whereas amplitudes were higher than 120 microV in only 22 of 299 A waves. Of these A waves, 68 were not constantly elicitable. There was a significant correlation between the number of A waves up to 50 ms poststimulus and the reduction in amplitude of the compound muscle action potential when elicited with proximal compared to distal stimulation in the peroneal (n = 26, P < 0.0005; Kendall's tau) and tibial nerves (n = 24, P < 0.002). Therefore, in GBS both conduction block and A waves are presumably signs of inflammatory nerve lesions. The existence of multiple A waves soon after onset of symptoms seems to be a sensitive sign of GBS.
Adolescent↗
Region-specific encoding of sensory and affective components of pain in the human brain: a positron emission tomography correlation analysis.
Brain imaging with positron emission tomography has identified some of the principal cerebral structures of a central network activated by pain. To discover whether the different cortical and subcortical areas process different components of the multidimensional nature of pain, we performed a regression analysis between noxious heat-related regional blood flow increases and experimental pain parameters reflecting detection of pain, encoding of pain intensity, as well as pain unpleasantness. The results of our activation study indicate that different functions in pain processing can be attributed to different brain regions; ie, the gating function reflected by the pain threshold appeared to be related to anterior cingulate cortex, the frontal inferior cortex, and the thalamus, the coding of pain intensity to the periventricular gray as well as to the posterior cingulate cortex, and the encoding of pain unpleasantness to the posterior sector of the anterior cingulate cortex.
Adult↗
Structural and functional organization of the fengycin synthetase multienzyme system from Bacillus subtilis b213 and A1/3.
BACKGROUND: Bacillus subtilis strains produce a broad spectrum of lipopeptides that are potent biosurfactants and have specific antimicrobial and antiviral activities. The cyclic lipodecapeptide fengycin is one such compound. Although the fengycin biosynthetic genes in B. subtilis 168 (pps genes) and F29-3 (fen genes) have been well characterized, only limited information is available about the biochemical features of the fengycin synthetase multienzyme system. RESULTS: Five multifunctional peptide synthetases (Fen1-5) that catalyze biosynthesis of the peptide portion of fengycin have been purified from crude extracts of the B. subtilis b213 and A1/3 strains. These enzymes activate all fengycin amino-acid components as aminoacyl adenylates or aminoacyl thioesters. Fen1, Fen2 and Fen3 are each approximately 286 kDa, Fen4 is approximately 400 kDa and Fen 5 is approximately 140kDa; each enzyme activates a different set of L-amino acids. A five-gene cluster (fen1-5) was detected in the B. subtilis A1/3 genome that shows high homology to the pps and fen genes in B. subtilis strains 168 and F29-3. Disruption of fen4 resulted in a loss of fengycin production. The fengycin synthetase enzymes isolated from B. subtilis b213 were assigned to the corresponding A1/3 fen genes by their amino-terminal sequences. CONCLUSIONS: The structural and functional organization of the fengycin synthetase system from B. subtilis b213 has been characterized in detail and correlated with the corresponding pps and fen genes in B. subtilis strains 168, A1/3 and F29-3. Biosynthesis of the peptide part of fengycin involves five multifunctional modular proteins that assemble the lipopeptide chain using a nonribosomal, multiple carrier thiotemplate mechanism.
Amino Acid Sequence↗
SELEDO: a 5-year long-term trial on the effect of selegiline in early Parkinsonian patients treated with levodopa.
The SELEDO (from selegiline plus levodopa) study was carried out as a randomized, prospective, placebo-controlled, double- blind, multicenter long-term, 5-year trial to evaluate the possible advantages of combining selegiline and levodopa in the early treatment of Parkinson's disease. One-hundred-and-sixteen patients were randomized either to selegiline or placebo. Before starting the study medication, the levodopa dose was titrated to the individual requirements of each patient. The primary study end point (time when levodopa had to be increased by >50% of the titrated dose) was reached in 23 of 59 patients in the selegiline group and 26 of 48 patients in the placebo group. At the end of the 5 years' treatment period the rates derived from a life-table analysis were 50.4% in the selegiline group and 74.1% in the placebo group (P = 0.027, log-rank test). The median time to reach the primary end point was 4.9 years in the selegiline group and 2.6 years in the placebo group. In patients treated with selegiline, the mean levodopa dose changed only slightly over the 5 years of treatment compared to the initially titrated dose, but rose markedly in the placebo group, where the dose of levodopa had to be adjusted earlier than in the selegiline group. At the same time, the lower levodopa dosage in the selegiline group was accompanied by at least equal therapeutic efficacy (which is necessary for an unambiguous interpretation). Subgroup analyses showed greater benefit for selegiline treated) patients in the earlier stages. Long-term side effects appeared later in the selegiline group, although the difference was not significant. The early combination of selegiline and levodopa proved to be clearly superior to levodopa monotherapy.
Adult↗
Low-frequency repetitive transcranial magnetic stimulation of the motor cortex in writer's cramp.
OBJECTIVE: To study the short-term effects of slow repetitive transcranial magnetic stimulation (rTMS) of the motor cortex on cortical excitability and handwriting in patients with writer's cramp. BACKGROUND: Cortical excitability of the primary motor cortex is abnormally enhanced in patients with writer's cramp. Therefore, reducing cortical excitability by low-frequency rTMS of the motor cortex might result in beneficial effects on handwriting in writer's cramp. DESIGN/METHODS: We studied the effects of subthreshold 1-Hz rTMS on motor threshold and cortico-cortical excitability using the paired-pulse technique in seven patients and seven controls. In another 16 patients and 11 age-matched controls we evaluated changes in cortical excitability by measuring the stimulus-response curve and the postexcitatory silent period before and after subthreshold 1-Hz rTMS. In addition, we analyzed the handwriting before and 20 minutes after 1-Hz rTMS. RESULTS: In the first experiment, low-frequency rTMS resulted in a normalization of the deficient cortico-cortical inhibition in the patients without affecting motor threshold. In the second experiment, 1-Hz rTMS resulted in a significant prolongation of the postexcitatory silent period without affecting the stimulus-response curve in the patient group. Moreover, the dystonic patients showed a significant reduction of mean writing pressure after subthreshold 1-Hz rTMS that was associated with clear but transient improvement in six patients. CONCLUSIONS: In some patients 1-Hz rTMS can reinforce deficient intracortical inhibition and may improve handwriting temporarily. Our data support the notion that reduced intracortical inhibition plays a part in the pathophysiology of focal dystonia.
Adult↗
Central pain after pontine infarction is associated with changes in opioid receptor binding: a PET study with 11C-diprenorphine.
Using 18F-fluorodeoxyglucose and 11C-diprenorphine positron emission tomography (PET), we investigated alterations in glucose metabolism and opioid receptor binding in a patient with central poststroke pain, which developed after a small pontine hemorrhagic infarction. In comparison with normal databases, reduced 11C-diprenorphine binding was more accentuated than the hypometabolism on the lateral cortical surface contralateral to the symptoms, and a differential abnormal distribution between the tracers was seen in pain-related central structures. These results show that 11C-diprenorphine PET provides unique information for the understanding of central poststroke pain.
Adult↗
Imaging brain activation induced by long trains of repetitive transcranial magnetic stimulation.
Using positron emission tomography (PET), we measured the relative changes in regional cerebral metabolic rate of glucose (rCMRglc) during 2 Hz repetitive transcranial magnetic stimulation (rTMS) of the left sensorimotor cortex (SM1) and during imitation of rTMS-induced arm movements. Such stimulation caused an rCMRglc increase of about 8% within the SM1. The relative rCMRglc increase within SM1 was significantly greater in magnitude and larger in area during voluntary imitation of rTMS-induced arm movements. Moreover, the rostral part of the SMA was significantly more activated by voluntary movements than during rTMS. Combining rTMS and PET has the potential to visualize rTMS-related net brain activation, and may open up new possibilities for functional network analysis by comparing willed brain activation with electromagnetic brain activation.
Adult↗
Continuous intrathecal baclofen infusions induced a marked increase of the transcranially evoked silent period in a patient with generalized dystonia.
We observed a marked prolongation of the transcranially evoked silent period during continuous intrathecal administration of high doses of the gamma-aminobutyric acid (GABA)B receptor agonist baclofen in a patient with generalized dystonia. Size of motor evoked potentials and central conduction time remained unchanged during intrathecal baclofen administration. The selective prolongation of the silent period during high-dose continuous intrathecal baclofen therapy supports the notion that GABA(B)-ergic intracortical interneurons play a part in the generation of the transcranially evoked silent period.
Adult↗
A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients.
Major histocompatibility class II (MHC-II) molecules are transmembrane proteins that have a central role in development and control of the immune system. They are encoded by a multigene family and their expression is tightly regulated. MHC-II deficiency (OMIM 209920) is an autosomal recessive immunodeficiency syndrome resulting from defects in trans-acting factors essential for transcription of MHC-II genes. There are four genetic complementation groups (A, B, C and D), reflecting the existence of four MHC-II regulators. The factors defective in groups A (CIITA), C (RFX5) and D (RFXAP) have been identified. CIITA is a non-DNA-binding co-activator that controls the cell-type specificity and inducibility of MHC-II expression. RFX5 and RFXAP are two subunits of RFX, a multi-protein complex that binds the X box motif of MHC-II promoters. Mutations in the genes encoding RFX5 (RFX5) or RFXAP (RFXAP) abolish binding of RFX (refs 7,8,12). Similar to groups C and D, group B is characterized by a defect in RFX binding, and although it accounts for the majority of patients, the factor defective in group B has remained unknown. We report here the isolation of RFX by a novel single-step DNA-affinity purification approach and the identification of RFXANK, the gene encoding a third subunit of RFX. RFXANK restores MHC-II expression in cell lines from patients in group B and is mutated in these patients. RFXANK contains a protein-protein interaction region consisting of three ankyrin repeats. Its interaction with RFX5 and RFXAP is essential for binding of the RFX complex to MHC-II promoters.
Amino Acid Sequence↗
Role of the human rostral supplementary motor area and the basal ganglia in motor sequence control: investigations with H2 15O PET.
The aim of this study was to investigate the functional anatomy of distributed cortical and subcortical motor areas in the human brain that participate in the central control of overlearned complex sequential unimanual finger movements. On the basis of previous research in nonhuman primates, a principal involvement of basal ganglia medial premotor loops [corrected] was predicted for central control of finger sequences performed automatically. In pertinent areas, a correlation of activation levels with the complexity of a motor sequence was hypothesized. H2 15O positron emission tomography (PET) was used in a group of seven healthy male volunteers [mean age 32.0 +/- 10.4 yr] to determine brain regions where levels of regional cerebral blood flow (rCBF) correlated with graded complexity levels of five different key-press sequences. All sequences were overlearned before PET and involved key-presses of fingers II-V of the right hand. Movements of individual fingers were kept constant throughout all five conditions by external pacing at 1-Hz intervals. Positive correlations of rCBF with increasing sequence complexity were identified in the contralateral rostral supplementary motor area (pre-SMA) and the associated pallido-thalamic loop, as well as in right parietal area 7 and ipsilateral primary motor cortex (M1). In contrast, while rCBF in contralateral M1 and [corrected] extensive parts of caudal SMA was increased compared with rest during task performance, significant correlated increases of rCBF with sequence complexity were not observed. Inverse correlations of rCBF with increasing sequence complexity were identified in mesial prefrontal-, medial temporal-, and anterior cingulate areas. The findings provide further evidence in humans supporting the notion of a segregation of SMA into functionally distinct subcomponents: although pre-SMA was differentially activated depending on the complexity of a sequence of learned finger movements, such modulation was not detectable in caudal SMA (except the most antero-superior part), implicating a motor executive role. Our observations of complexity-correlated rCBF increases in anterior globus pallidus suggest a specific role for the basal ganglia in the process of sequence facilitation and control. They may act to filter and focus input from motor cortical areas as patterns of action become increasingly complex.
Adult↗
A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes.
Microbial superantigens (SAGs) have been implicated in the pathogenesis of human autoimmune diseases. Preferential expansion of the Vveta7 T cell receptor positive T cell subset in patients suffering from acute-onset type I diabetes has indicated the presence of a surface membrane-bound SAG. Here, we have isolated a novel mouse mammary tumor virus-related human endogenous retrovirus. We further show that the N-terminal moiety of the envelope gene encodes an MHC class II-dependent SAG. We propose that expression of this SAG, induced in extrapancreatic and professional antigen-presenting cells, leads to beta-cell destruction via the systemic activation of autoreactive T cells. The SAG encoded by this novel retrovirus thus constitutes a candidate autoimmune gene in type I diabetes.
Adolescent↗
Magnetic resonance ventriculography with gadolinium DTPA: report of two cases.
We report intrathecal use of gadolinium DTPA for MRI of the cerebrospinal fluid (CSF). In two patients with leptomeningeal carcinomatosis, we injected 0.01 mmol gadolinium DTPA into the lateral ventricle via an Ommaya device. Coronal T1-weighted images of the head were obtained at 0.2 T prior to and after injection. There was pronounced enhancement of CSF close to the injection site, allowing good delineation of CSF and surrounding brain tissue. No side effects occurred. MRI with intrathecal administration of highly diluted gadolinium DTPA may be a promising alternative to conventional investigation of CSF-filled cavities using iodinated X-ray contrast media or radionuclides.
Antineoplastic Combined Chemotherapy Protocols↗
Central motor processing in Huntington's disease. A PET study.
Repeated PET cerebral blood flow measurements using H2(15)O were performed in 13 patients with confirmed Huntington's disease and nine age-matched controls. The activation paradigm consisted of an externally triggered finger opposition task (1.5 Hz) with the dominant hand, the control condition being the auditory input. In the patients with Huntington's disease, impaired activity of the striatum and its frontal motor projection areas (rostral supplementary motor area, anterior cingulate and premotor cortex) could be demonstrated along with enhanced activity mainly in parietal areas during movement. The results suggest that the pathology of Huntington's disease causes impairment of the output part of the basal ganglia-thalamo-cortical motor circuit and may induce a compensatory recruitment of additional accessory motor pathways involving the parietal cortex.
Adult↗
A T7 promoter-specific, inducible protein expression system for Bacillus subtilis.
The adaptation and application of the Escherichia coli T7 RNA polymerase system for regulated and promoter-specific gene expression in Bacillus subtilis is reported. The expression cassette used in Bacillus subtilis was tightly regulated and T7 RnA polymerase (T7 RNAP)appeared 30 minutes after induction. The efficiency of T7 promoter-specific gene expression in B.subtilis was studied using one secretory and two cytosolic proteins of heterologous origin. The accumulation of E. coli beta-galactosidase, as well as a 1,4-beta-glucosidase from Thermoanaerobacter brockii in B. subtilis after T7 RNAP induction was strongly enhanced by rifampicin inhibition of host RNAP activity. The alpha-amylase of Thermactinomyces vulgaris, a secretory protein, was found to accumulate in the culture supernatant up to levels of about 70 mg/l 10-20 h after T7 RNAP induction, but was also deposited in cellular fractions. The addition of rifampicin inhibited chi-amylase secretion, but unexpectedly, after a short period, also prevented its further (intra)cellular accumulation.
Bacillus subtilis↗
Acute overdose of intrathecal baclofen.
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Adult↗