PubMed Health⌕ Search

Biomedical subjects

B Conrad

Publications and source records attributed to B Conrad.

At least 73 records · Page 4Linked to original sources
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↗
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

Comparison of various coils used for magnetic stimulation of peripheral motor nerves: physiological considerations and consequences for diagnostic use.

We compared the ability of 4 magnetic coils to activate peripheral nerves in healthy subjects. No differences in motor threshold intensities were found between the coils, but the intensities needed to elicit maximum compound muscle action potential (CMAP) amplitudes were different. For superficial nerves maximum CMAPs in comparison with electrical stimulation were usually but not always found. CMAPs were at their maximum only when the direction of induced current flowed from proximal to distal and when a certain part of the coil was over the nerve. Distal nerve stimulation was time consuming. Due to artifacts many stimuli were necessary and sometimes no maximum CMAP could be elicited. CMAPs were much less sensitive to position changes of the coil than to changes in an electrical stimulator. Small circular coils were superior to larger coils in terms of the lower intensities necessary to elicit maximum CMAPs, better focusing of the stimulus, and less artifacts. For deep nerves amplitudes were always submaximal. Coactivation of nearby nerves and underlying muscles was another main drawback especially at proximal sites and for coils of large diameter. Despite better focusing, double coils are less useful due to their great diameter. Magnetic stimulation cannot replace electrical neurography at the moment, even if different coils are used at different sites of stimulation.

Action Potentials↗
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

Cerebral perfusion during sleep-disordered breathing.

Snoring, a leading symptom of the sleep apnoea syndrome (SAS), has been reported to be one of the risk factors for sleep-related cerebral strokes. Episodes of apnoea are accompanied by hypoxaemia as well as hypercapnia. As CO2 constitute a major regulatory factor controlling cerebral blood flow, it is likely that changes in cerebral perfusion are to be found in patients with SAS, which may be related to nocturnal stroke. A computer-assisted pulsed (2 mHz) Doppler ultrasonography system has been modified for continuous long-term and on-line recording of cerebral haemodynamics together with simultaneous polysomnography, continuous blood pressure recordings, and measurement of the end-expiratory CO2. The dynamics of cerebral blood flow velocity (CBFV) during sleep were measured in the right middle cerebral artery in 10 SAS patients. CBFV showed a characteristic nocturnal pattern with decreases during non-rapid eye movement (NREM) sleep and increases during REM sleep. Changes in sleep stage patterns as well as awakenings from NREM sleep were not regularly accompanied by corresponding changes in CBFV. Dramatic increases in CBFV could be observed during apnoeic episodes, with maximum increases during REM sleep. CO2 reactivity and changes in CBFV related to apnoea duration were markedly increased during sleep compared with the waking state in SAS patients. The dynamic feature of CBFV in relation to sleep patterns reflects quantitative uncoupling between cerebral electrical activity and cerebral perfusion during sleep in SAS patients as has been previously reported for normal subjects (Hajak et al. 1994). It supports a dissociation in the activity of central regulatory mechanisms during human sleep which might cause abnormal cerebral perfusion under certain circumstances. The increased CO2 reactivity during sleep in SAS suggests a 'hypersensitivity' of intracranial vasoactive receptors and/or disturbances in the central autonomic control of cerebrovascular functions. It may be concluded that, under certain conditions, the interaction of decreased cerebral perfusion in SAS patients with sleep-related cerebral perfusion patterns and haemodynamic changes during apnoeic episodes might lead to a critical reduction in cerebral perfusion.

Journal Article↗