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Biomedical subjects

W Reith

Publications and source records attributed to W Reith.

At least 91 records · Page 5Linked to original sources
PubMed2001

Low field-low cost: can low-field magnetic resonance systems replace high-field magnetic resonance systems in the diagnostic assessment of multiple sclerosis patients?

As low-field MR imaging is becoming a widely used imaging technique, we aimed at a prospective assessment of differences in imaging quality between low- and high-field MR imaging in multiple sclerosis patients possibly interfering with diagnostic or therapeutic decision making. Twenty patients with clinically proven multiple sclerosis were examined with optimized imaging protocols in a 1.5- and a 0.23-T MR scanner within 48 h. Images were assessed independently by two neuroradiologists. No statistically significant interrater discrepancies were observed. A significantly lower number of white matter lesions could be identified in low-field MR imaging both on T1- and on T2-weighted images (T2: high field 700, low field 481; T1: high field 253, low field 177). A total of 114 enhancing lesions were discerned in the high-field MR imaging as opposed to 45 enhancing lesions in low-field MR imaging. Blood-brain barrier disruption was identified in 11 of 20 patients in the high-field MR imaging, but only in 4 of 20 patients in low-field MR imaging. Since a significantly lower lesion load is identified in low-field MR imaging than in high-field MR imaging, and blood-brain barrier disruption is frequently missed, caution must be exercised in interpreting a normal low-field MR imaging scan in a patient with clinical signs of multiple sclerosis and in interpreting a scan without enhancing lesions in a patient with known multiple sclerosis and clinical signs of exacerbation.

Adult↗
PubMed2001

Demonstration of periventricular brain motion during a Valsalva maneuver: description of technique, evaluation in healthy volunteers and first results in hydrocephalic patients.

There has long been a need for a sensitive and predictive parameter in the evaluation of hydrocephalic patients. Our goal was to assess ventricular response to a Valsalva maneuver as a potential method of studying patients with hydrocephalus. Twenty-five healthy volunteers and 5 patients with communicating hydrocephalus were examined with an axial and 10 volunteers with an axial, coronal and sagittal true fast imaging steady precession (FISP) sequence in a 1.5-T clinical MR scanner (TR 4.8 ms, TE 2.3 ms, flip angle 70 degrees, slice thickness 5 mm, field of view 330 mm, 3 slices). Images were assessed both as dynamic images in cine mode and by measuring lateral ventricular size over time. All volunteers showed marked periventricular brain motion. The lateral ventricular area was reduced under the Valsalva maneuver by an average of 18% (SD 7) in healthy volunteers, while remaining practically constant in the patient group. Differences were statistically significant with a p<0.0001. The Valsalva maneuver leads to periventricular brain motion, which can be consistently detected by a true FISP sequence. Our method proved to be an easy and reliable method with a capacity to identify hydrocephalic patients.

Adult↗
PubMed2001

Primary immunodeficiency mutation databases.

Primary immunodeficiencies are intrinsic defects of immune systems. Mutations in a large number of cellular functions can lead to impaired immune responses. More than 80 primary immunodeficiencies are known to date. During the last years genes for several of these disorders have been identified. Here, mutation information for 23 genes affected in 14 immunodefects is presented. The proteins produced are employed in widely diverse functions, such as signal transduction, cell surface receptors, nucleotide metabolism, gene diversification, transcription factors, and phagocytosis. Altogether, the genetic defect of 2,140 families has been determined. Diseases with X-chromosomal origin constitute about 70% of all the cases, presumably due to full penetrance and because the single affected allele causes the phenotype. All types of mutations have been identified; missense mutations are the most common mutation type, and truncation is the most common effect on the protein level. Mutational hotspots in many disorders appear in CPG dinucleotides. The mutation data for the majority of diseases are distributed on the Internet with a special database management system, MUTbase. Despite large numbers of mutations, it has not been possible to make genotype-phenotype correlations for many of the diseases.

Alleles↗
PubMed2001

How do concentration and dosage of the contrast agent affect the signal change in perfusion-weighted magnetic resonance imaging? A computer simulation.

In this study we investigated the effect of varying both concentration and dosage of an intravenously administered MR contrast agent on the concentration-time curve in brain tissue. Aside from injection time and injection rate, our model considers the distribution of transit-time between injection site and brain but it is independent from pulse rate, heart volume or other circulation parameters. The width of the transit-time distribution and the concentration-time course in the brain were computed according to indicator dilution theory. We found that increasing the dosage of the administered contrast agent raises the maximum concentration of the agent in the brain, particularly if the injection time is short. Increasing the concentration of the agent (at fixed dosage and injection rate) also increases maximum concentration in the brain capillaries, particularly if the injection time is long. This increase, however, is less than that achieved by raising the dosage.

Animals↗
PubMed2001

Effect of moderate hypothermia on experimental severe subarachnoid hemorrhage, as evaluated by apparent diffusion coefficient changes.

OBJECTIVE: The aims of this study were to investigate the early changes in the mean apparent diffusion coefficient (ADC) after severe subarachnoid hemorrhage (SAH), as a marker of ischemic damage, and to examine the effects of moderate hypothermia, induced at various time points, on ADC changes. METHODS: ADC maps were calculated from diffusion-weighted, blipped-epi, spin echo, magnetic resonance imaging sequences (2.35-T BIOSPEC 24/40 scanner; Bruker Medizin Technik GmbH, Karlsruhe, Germany) for 21 anesthetized (0.45-1% halothane, temperature-adjusted/30% oxygen/69% nitrogen) and ventilated Wistar rats. After baseline scanning, bolus injection of 0.5 ml of autologous arterial blood or artificial cerebrospinal fluid (control group), into the cisterna magna, was performed. Serial scanning was performed for 3 hours after injection, using normothermic or hypothermic (32 degrees C) rats. In an additional series of experiments, hypothermia was initiated either immediately or 60 minutes after normothermic SAH. The water contents of the removed brains were calculated using the wet/dry weight method. RESULTS: The ADC values did not change in the control group but decreased to 88.6+/-5.2% (P < 0.05 versus baseline) after SAH and remained significantly decreased throughout the experiment in normothermia. An injection of blood during hypothermia caused an initial decrease in ADC to 96.1+/-5.6% (P < 0.05 versus baseline); values continuously increased and reached normal levels within 60 minutes. Delayed hypothermia also normalized ADC values within the observation period. The brain water content in the control group was 80.3+/-0.1%, that after SAH in normothermia was 81.1+/-0.7%, and that after SAH in hypothermia was 79.3+/-0.5%. CONCLUSION: This model of severe SAH in rats causes significant ADC changes, which are reversible by application of moderate hypothermia even when it is induced after a 60-minute delay. These findings support the concept of moderate hypothermia exerting a neuroprotective effect in severe SAH.

Animals↗
PubMed2001

Expression of the three human major histocompatibility complex class II isotypes exhibits a differential dependence on the transcription factor RFXAP.

Major histocompatibility complex class II (MHCII) molecules play a pivotal role in the immune system because they direct the development and activation of CD4(+) T cells. There are three human MHCII isotypes, HLA-DR, HLA-DQ, and HLA-DP. Key transcription factors controlling MHCII genes have been identified by virtue of the fact that they are mutated in a hereditary immunodeficiency resulting from a lack of MHCII expression. RFXAP-one of the factors affected in this disease-is a subunit of RFX, a DNA-binding complex that recognizes the X box present in all MHCII promoters. To facilitate identification of conserved regions in RFXAP, we isolated the mouse gene. We then delimited conserved domains required to restore endogenous MHCII expression in cell lines lacking a functional RFXAP gene. Surprisingly, we found that 80% of RFXAP is dispensable for the reactivation of DR expression. Only a short C-terminal segment of the protein is essential for this isotype. In contrast, optimal expression of DQ and DP requires a larger C-terminal segment. These results define an RFXAP domain with an MHCII isotype-specific function. Expression of the three MHCII isotypes exhibits a differential requirement for this domain. We show that this is due to a differential dependence on this domain for promoter occupation and recruitment of the coactivator CIITA in vivo.

Amino Acid Sequence↗
PubMed2001

The bare lymphocyte syndrome and the regulation of MHC expression.

The bare lymphocyte syndrome (BLS) is a hereditary immunodeficiency resulting from the absence of major histocompatibility complex class II (MHCII) expression. Considering the central role of MHCII molecules in the development and activation of CD4(+) T cells, it is not surprising that the immune system of the patients is severely impaired. BLS is the prototype of a "disease of gene regulation." The affected genes encode RFXANK, RFX5, RFXAP, and CIITA, four regulatory factors that are highly specific and essential for MHCII genes. The first three are subunits of RFX, a trimeric complex that binds to all MHCII promoters. CIITA is a non-DNA-binding coactivator that functions as the master control factor for MHCII expression. The study of RFX and CIITA has made major contributions to our comprehension of the molecular mechanisms controlling MHCII genes and has made this system into a textbook model for the regulation of gene expression.

Animals↗
PubMed2001

[Lumbar arachnoiditis as differential chronic spinal symptoms diagnosis].

Lumbar epiduro-arachnoiditis is an infectious disease of the three mengial layers. It is often caused by surgical interventions on the spine. In this survey etiologic factors, clinical symptoms and radiological findings are compared. The radiologic classification of Delamater is described by three clinical cases. The diagnostic value of different procedures such as myelography, postmyelographic computed tomography and MR imaging is evaluated.

Arachnoid↗
PubMed2000

Dissection of functional NF-Y-RFX cooperative interactions on the MHC class II Ea promoter.

Transcription of major histocompatibility complex (MHC) class II genes depends upon the trimeric complexes RFX and NF-Y binding to the conserved X-Y promoter elements. We produced and purified the RFX subunits from Escherichia coli, reconstituted DNA-binding to the mouse Ea X box and dissected the interactions with NF-Y. RFX and NF-Y do not interact in solution, but make cooperative interactions in EMSA: a minimal NF-Y, composed of the evolutionary conserved domains, is sufficient and the RFXAP N-terminal half is expendable. Altering the X-Y distance abolishes cooperativity, indicating that DNA imposes severe spatial constraints. When tested on a highly positioned nucleosome, RFX binds DNA well and NF-Y does not increase its affinity further. Transfections of NF-Y subunits, but not RFX, in class II negative cells improves basal transcription and coexpression of the two activators has a synergistic effect, while modestly increasing CIITA-mediated activation. These results show that interactions between the two trimers on DNA are key to MHC class II expression.

Animals↗
PubMed2000

CIITA is a transcriptional coactivator that is recruited to MHC class II promoters by multiple synergistic interactions with an enhanceosome complex.

By virtue of its control over major histocompatibility complex class II (MHC-II) gene expression, CIITA represents a key molecule in the regulation of adaptive immune responses. It was first identified as a factor that is defective in MHC-II deficiency, a hereditary disease characterized by the absence of MHC-II expression. CIITA is a highly regulated transactivator that governs all spatial, temporal, and quantitative aspects of MHC-II expression. It has been proposed to act as a non-DNA-binding transcriptional coactivator, but evidence that it actually functions at the level of MHC-II promoters was lacking. By means of chromatin immunoprecipitation assays, we show here for the first time that CIITA is physically associated with MHC-II, as well as HLA-DM, Ii, MHC-I, and beta(2)m promoters in vivo. To dissect the mechanism by which CIITA is recruited to the promoter, we have developed a DNA-dependent coimmunoprecipitation assay and a pull-down assay using immobilized promoter templates. We demonstrate that CIITA recruitment depends on multiple, synergistic protein-protein interactions with DNA-bound factors constituting the MHC-II enhanceosome. CIITA therefore represents a paradigm for a novel type of regulatory and gene-specific transcriptional cofactor.

B-Lymphocytes↗
PubMed2000

Structure of the winged-helix protein hRFX1 reveals a new mode of DNA binding.

Regulatory factor X (RFX) proteins are transcriptional activators that recognize X-boxes (DNA of the sequence 5'-GTNRCC(0-3N)RGYAAC-3', where N is any nucleotide, R is a purine and Y is a pyrimidine) using a highly conserved 76-residue DNA-binding domain (DBD). DNA-binding defects in the protein RFX5 cause bare lymphocyte syndrome or major histocompatibility antigen class II deficiency. RFX1, -2 and -3 regulate expression of other medically important gene products (for example, interleukin-5 receptor alpha chain, IL-5R alpha). Fusions of the ligand-binding domain of the oestrogen receptor with the DBD of RFX4 occur in some human breast tumours. Here we present a 1.5 A-resolution structure of two copies of the DBD of human RFX1 (hRFX1) binding cooperatively to a symmetrical X-box. hRFX1 is an unusual member of the winged-helix subfamily of helix-turn-helix proteins because it uses a beta-hairpin (or wing) to recognize DNA instead of the recognition helix typical of helix-turn-helix proteins. A new model for interactions between linker histones and DNA is proposed.

Amino Acid Sequence↗
PubMed2000

Dendritic cells and differential usage of the MHC class II transactivator promoters in the central nervous system in experimental autoimmune encephalitis.

In the normal central nervous system (CNS) expression of MHC class II is minimal, but has been found to be highly up-regulated on microglia cells in experimental autoimmune encephalitis (EAE). Here we used the EAE model to examine the regulation of expression of the class II transactivator (CIITA), which is required for activation of MHC class II genes. EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55. CIITA mRNA form I (specific for dendritic cells) and form IV (IFN-gamma inducible) but not form III (B cell specific) were detected in brain and spinal cord of mice with acute EAE. In unimmunized or mock-immunized mice, none of the three CIITA forms was found to be induced. Dendritic cells (DC) were identified by immunostainings for CD11c in perivascular and meningeal cell infiltrates in EAE spinal cord and brain. Time-course analysis showed (1) the appearance of DC in the CNS shortly before onset of disease, (2) the recruitment of CD11b cells occuring much earlier and (3) the absence of CIITA and MHC class II expression in these CD11b+ cells at preclinical stages.

Animals↗
PubMed2000

[Cerebral vasculitis as a concomitant neurological illness in Crohn's disease].

In Crohn's disease, some concomitant neurological illnesses such as cerebral ischemia following arterial or venous thrombosis, subacute combined degeneration of the spinal cord following malabsorption of vitamin B12 or folic acid, opticus neuropathy, and polyneuropathy have been described. Cerebral vasculitis secondary to Crohn's disease seems to be a very rare phenomenon. We report on three such cases in three female patients (aged 26, 29, and 61 years). All patients became symptomatic with a hemiparesis; one complained additionally of a speech disorder, headache, and intermittent loss of orientation. In CT and MRI scans, multiple lesions were detected; cerebral angiography showed multiple stenoses of middle- and large-sized vessels that were compatible with cerebral vasculitis. Serologic tests concerning vasculitis were inconspicuous at that time. Under anticoagulation (in two cases) and immunosuppressive therapy, neurologic symptoms disappeared. In the following 6 to 12 months, no new neurological symptoms appeared. In two cases, Doppler sonographic controls showed stationary and, in one case, progressive intracranial stenoses. Since autoimmunologically caused inflammatory bowel diseases might be associated with vasculitis of other organs, the appearance of cerebral vasculitis secondary to Crohn's disease is a possible organ manifestation by inflamed vessels.

Adult↗
PubMed2000

[Herpes simplex virus encephalitis: neuroradiologic differential diagnosis].

Herpes simplex virus encephalitis (HSE) is the most frequent viral encephalitis, as a rule with the starting point and centre within the temporal lobe. If untreated, HSE is usually fatal, thus diagnosis has to be established rapidly. Treatment with Acyclovir should begin as soon as possible. As MRI is extremely sensitive in detecting the early inflammatory changes, it should be initially performed, especially as in the early stadium CT may be unspecific. We recommend the following examination protocol: coronar T1-weighted MR imaging before and after administration of gadopentetate dimeglumine, coronar FLAIR sequence and axial T2-weighted imaging. The diagnostic proof is to show the evidence of viral DNA by polymerase chain reaction (PCR) in cerebrospinal liquor.

Acyclovir↗
PubMed2000

[Neuroradiological aspects of encephalitis disseminata].

Magnetic resonance imaging (MRI) has developed without doubt to the most important investigation method in multiple sclerosis. MRI is very sensitive to detect MS lesions but unfortunately of limited specificity. The purpose of this review is 1. to work up the MRI characteristics of MS lesions, 2. to derive recommendations for MRT-protocolls for daily radiological work and 3. to discuss new MR developments. MS lesions in the acute inflammatory stage show first an enhancement of GD-DTPA due to break down of the blood brain barrier and develop a T2-hyperintensity due to an edema. The following disease course is categorized in a phase of reparation and remyelinisation respectively, of gliosis and a defect stage. MS-plaques in the remyelinisation and gliotic phase appear as hyperintens lesions on T2-weighted scans. Chronic MS lesions with a defect are also T2-hyperintens and demonstrate additionally due to severe axonal loss a hypointensity on short TR SE scans. MS lesions exhibit a characteristic distribution. They are found typically periventricular, in the corpus callosum and at the calloso-septal interface, cortico-subcortical and infratentorial. The most important MR criteria to predict conversion from suspected (CSMS) to clinical definite MS (CDMS) are GD-DTPA enhancement and juxtacortical lesion localisation followed by the parameter periventricular and infratentorial localisation. Based on guidelines for the use of MRI in drug studies and on equivalent recommendations for the routine diagnostic we suggest rational and economic MRT protocols for cerebral, spinal, and N. opticus investigations. Such standardised protocols shall help to make MRI investigations more efficient and better comparable. New MR developments include measurement of magnetisation transfer and T2-relaxation, diffusion weighted imaging, proton MR spectroscopy, and quantification of lesion load. These methods can analyse more specifically tissue changes in MS plaques and yet can reveal changes in normal appearing white matter.

Brain↗