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Biomedical subjects

B Conrad

Publications and source records attributed to B Conrad.

At least 55 records · Page 3Linked to original sources
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

Secondary parkinsonism due to focal substantia nigra lesions: a PET study with [18F]FDG and [18F]fluorodopa.

We present a 71 year old woman with predominantly right sided parkinsonism of sudden onset, but without tremor. Magnetic resonance imaging (MRI) depicted lesions affecting the substantia nigra (SN) bilaterally, but more pronounced on the left side. There were no other discernible structural lesions. Using positron emission tomography (PET), we investigated regional cerebral metabolic rate of glucose (rCMRG) using the tracer [18F]-fluorodeoxyglucose (FDG), and striatal dopa decarboxylase capacity using the tracer [18F]-L-6-fluorodopa (FDOPA). The degree and pattern of distribution of FDOPA uptake reductions (putamen > caudate nuclei) were similar to those in idiopathic Parkinson's disease (PD). FDG uptake also revealed similar changes (reductions in frontal cortex and cerebellum, but increases in thalamus), except for putamen which showed reduced rCMRG. In conclusion, the absence of tremor at rest accords with experimental SN lesions. The PET findings in this atypical condition are explained in terms of deafferentation of various brain regions involved in motor control. Furthermore, they illustrate the metabolic effects related to acute focal lesions of the SN as opposed to the progressive degeneration in idiopathic PD and may serve to help unravel the complicated pathophysiology underlying these conditions.

Aged↗
PubMed1996

Blood-CSF barrier integrity in multiple sclerosis.

INTRODUCTION: In about 20% of MS patients an increased CSF/serum albumin quotient (QAlb) has been observed. The reason for this blood-CSF barrier dysfunction is yet unclear. SUBJECTS AND METHODS: QAlb values from 48 MS patients in relapse were correlated with parameters of active CNS lesions as measured by gadolinium-DTPA MRIs. QAlb values from 20 MS patients without relapse served as controls. RESULTS: Mean QAlb values (x 10(3) of a group with spinal cord lesions (7.6 +/- 3.6; n = 16) differed significantly from those of a control group (4.6 +/- 1.5; n = 20; p < 0.005) as well as from those of a group with supratentorial lesions (5.0 +/- 1.8; n = 18; p < 0.05), and were higher than those of a group with infratentorial lesions (5.8 +/- 2.8; n = 14). QAlb values of patients with a spinal lesion tended to decrease with increasing time intervals between onset of relapse and lumbar puncture. CONCLUSION: The data is in consent with the present knowledge on flow dynamics of both extracellular fluid and CSF. As a clinical consequence, increased QAlb values in MS patients may hint at an active spinal or, less likely, infratentorial lesion.

Adult↗
PubMed1996

Lasting reduction of severe spasticity after ending chronic treatment with intrathecal baclofen.

OBJECTIVE: To investigate whether the dose of intrathecal baclofen necessary for a sufficient reduction of muscle tone and spasms changes during treatment of severe spasticity. METHODS: A group of 27 patients received intrathecal baclofen for 61 (SD 18) months. RESULTS: Spasticity remained absent or strongly reduced after stopping the intrathecal baclofen infusion in seven patients. The dose of baclofen could be reduced to 40% of that dose which was originally necessary in 10 patients. The dose remained the same or increased slightly in 10 patients. Possible reasons for the continuing reduction of spasticity after terminating long term intrathecal baclofen infusion in some patients could be: lasting morphological changes in spinal cord neurons by second messenger controlled modulation of gene expression, a toxic effect of baclofen on spinal neurons, muscular atrophy, inflammation due to the catheter, or progression of multiple sclerosis. CONCLUSIONS: A higher initial daily dose of intrathecal baclofen might lead to a faster, lasting suppression of spasticity and the development of spastic symptoms might even be prevented by pre-emptive treatment with baclofen in patients with newly acquired lesions of the spinal cord.

Adult↗
PubMed1996

Cerebrotendinous xanthomatosis without tendon xanthomas mimicking Marinesco-Sjoegren syndrome: a case report.

A 39 year old patient with cerebellar signs, juvenile cataracts, and dull normal intelligence had cerebrotendinous xanthomatosis without tendon xanthomas, diagnosed previously as Marinesco-Sjoegren syndrome. Cerebrotendinous xanthomatosis was proved by a greatly increased excretion of bile alcohols in the patient's urine. Cerebrotendinous xanthomatosis is a sterol storage disorder due to an autosomal recessive inherited defect of sterol 27-hydroxylase characterised by high cholestanol concentration in multiple tissues. If tendon xanthomas are not present, a diagnosis of cerebrotendinous xanthomatosis will often not be made, unless biochemical tests are performed. The clinical features of cerebrotendinous xanthomas strongly resembles Marinesco-Sjoegren syndrome. Marinesco-Sjoegren syndrome is a autosomal recessive disorder characterised by the triad cerebellar ataxia, congenital cataract, and mental retardation. Although a late onset after the first decade of life favours cerebrotendinous xanthomatosis as the underlying disease, a definite distinction between cerebrotendinous xanthomatosis without tendon xanthomas and Marinesco-Sjoegren syndrome based on clinical presentation may be difficult. It is considered that some patients with Marinesco-Sjoegren syndrome reported in the medical literature had cerebrotendinous xanthomatosis without tendon xanthomas. This is of crucial clinical relevance, because, by contrast with Marinesco-Sjoegren syndrome, treatment for cerebrotendinous xanthomatosis is already available.

Adult↗
PubMed1996

[Intracranial blood flow parameters in cerebral functional changes and cognitive cerebral performance].

Extensive studies have revealed a close relationship between neuronal activity and regional cerebral blood flow. However, SPECT and PET, the technologies most commonly used in these studies, are of limited value for assessment of the dynamics of cerebral blood flow changes at different states of functional brain activity. The introduction of transcranial Doppler sonography and the extended application of stimuli presentation and perception have now been added to the investigator's armamentarium. Simple sensory stimulation (visual, acoustic and tactile) and complex mental tasks (viewing of complex pictures, tactile differentiation of objects) changed the blood flow velocity in the basal intracranial arteries. These changes corresponded to the current concepts of functional cortical organization. The magnitude of the flow velocity increases upon visual stimulation was dependent on the complexity of the stimuli used, and was up to 38% in our studies. The introduction of continuous and bilateral simultaneous Doppler recordings, the calculation of mean flow velocity from cardiac cycle to cardiac cycle and a specially designed averaging method for data analysis allowed effective elimination of non-specific influences and made it possible to demonstrate rapid changes of perfusion in both middle cerebral artery territories in direct response to hemisphere-specific tasks. These changes were correlated with known functional cerebral asymmetries. A language task, for instance, was associated with a significantly larger flow velocity increase in the middle cerebral artery of the dominant hemisphere than in the corresponding artery of the non-dominant hemisphere (5.2 +/- 1,8% vs 3.0 +/- 1.8%, p < 0.001). The excellent time resolution of this technology made it possible to record hemodynamic changes taking place in response to modifications of neuronal activity within less than 1 s. The shortest time interval between stimulus presentation and the first significant increase in flow velocity was on average 717 +/- 191 ms. The latency of less than 1 s suggest that the coupling between alterations of neuronal activity and the regional cerebral blood flow response is mediated by an remarkably rapid mechanism.

Arousal↗
PubMed1996

[Isolation and cryopreservation of human islets of Langerhans].

Islet transplantation represents an alternative to whole pancreas transplantation for the treatment of patients suffering from diabetes type I. The transplantation of a sufficient number of islets is an essential condition for successful allograft. Islet cryopreservation allows the storage of islet preparations for subsequent pooling, at the time of transplantation, of cryopreserved islets with a fresh preparation in order to increase the mass of transplanted pancreatic endocrine tissue. From May 1994 to April 1995, islets were isolated from 22 human pancreases using a modified automated method, and 19 preparations were cryopreserved. The function of cryopreserved islets was tested in vitro (static incubation and perifusion). The results of static incubation experiments confirmed that the insulin secretion of cryopreserved human islets in response to glucose stimulation was comparable to the response of islets that have not been frozen. In static incubation experiments, the mean (+/- SEM) insulin secretion of islets, prior to cryopreservation, was 239.3 (+/- 58.9) and 479.5 (+/- 59.5) pg/islet/15 min at 2.8 mM glucose and 16.7 mM glucose respectively. The mean (+/- SEM) insulin secretion of cryopreserved islets was 274 (+/- 103.2) and 468.5 (+/- 191.9) pg/islet/15 min at 2.8 mM and 16.7 mM glucose respectively. The perifusion experiments also demonstrated a significant increase of insulin secretion from cryopreserved islets perifused with a stimulating glucose concentration. Our experiments allow us to envisage the use of cryopreserved islet preparations for allotransplantation in diabetic patients.

Adult↗
PubMed1996

Combined islet-lung transplantation in a cystic fibrosis patient.

The prevalence of insulin-dependent diabetes mellitus (IDDM) in cystic fibrosis patients ranges from 2 to 8% and glucose intolerance up to 15%. In recent years, lung transplantation has helped to prolong life expectancy of cystic fibrosis patients and represents 10 to 30% of all indications for lung transplantation. The postoperative need for immunosuppressive therapy using diabetogenic agents has decompensatory effects on glucose regulation and will probably increase the number of insulin-dependent cystic fibrosis patients. We report the case of an insulin-dependent cystic fibrosis patient transplanted with a combined islet-lung allograft. The pre-transplantation C-peptide level was below 0.04 nmol/l and preoperative insulin requirement was some 100 U per day. A sequential bipulmonary lung transplantation was performed and, using the pancreas of the same donor, we isolated and purified the islets of Langerhans by a modified automated method. We obtained 232,200 islets equivalent, which were injected into the liver by portal embolization. The postoperative course was uncomplicated, the insulin requirement decreased to 50% of the preoperative need and the C-peptide value increased to normal values and remained with the normal range during a follow-up period of 15 months. In conclusion, we believe that, besides type I diabetic patients, insulin-dependent cystic fibrosis patients with a negative C-peptide value could also be good candidates for combined islet-lung allotransplantation.

Adult↗