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Biomedical subjects

W Reith

Publications and source records attributed to W Reith.

At least 127 records · Page 7Linked to original sources
PubMed1998

Spiral CT vs incremental CT: is spiral CT superior in imaging of the brain?

The aim of this study was to evaluate image quality of spiral CT of the brain as compared with incremental CT using identical scanning parameters. Incremental or spiral cranial CT was performed on 46 consecutive, randomized patients with non-traumatic disease of the brain on a Siemens (Erlangen, Germany) Somatom Plus 4. Evaluation was done in a randomized blinded way by two experienced radiologists. Different anatomical structures, image noise, and artifacts were scaled 1 (bad) to 4 (very good). Statistical analysis was done using the F-test of variance for partial sums of squares as well as Student's t-test. Incremental CT was superior to spiral CT for evaluation of the internal capsule, supratentorial artifacts, gray/white matter differentiation, and image noise. No statistically significant differences were seen for evaluation of the pons, infratentorial artifacts, and eye muscles. With identical scanning parameters incremental CT is superior to spiral CT in the assessment of small, complex structures in a low-contrast setting. No differences are seen for larger structures or small structures in a medium-contrast range. Artifacts localized close to the skull in spiral CT can easily mimic hemorrhage in traumatized patients. Spiral CT should therefore only be used for CT angiography and if 3D reconstructions are needed.

Artifacts↗
PubMed1998

Residual MHC class II expression on mature dendritic cells and activated B cells in RFX5-deficient mice.

Patients with major histocompatibility complex class II (MHC-II) deficiency are known to carry mutations in either the RFX complex or the trans-activator CIITA. While the pivotal role of CIITA for MHC-II gene transcription is supported by the essential absence of MHC-II molecules in CIITA-deficient mice, we demonstrate here that RFX5-/- mice retain expression of MHC-II in thymic medulla, mature dendritic cells, and activated B cells. Nevertheless, RFX5-/- mice develop a severe immunodeficiency due to the lack of MHC-II in thymic cortex, failure of positive selection of CD4+ T cells, and absence of MHC-II on resting B cells and resident or IFNgamma-activated macrophages. This differential requirement for CIITA and RFX5 in subsets of antigen-presenting cells may be specific for the mouse; it may, however, also exist in humans without having been noticed so far.

Animals↗
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

Genetic and molecular definition of complementation group D in MHC class II deficiency.

Four complementation groups, A, B, C and D, have been described among cell lines defective in the coordinate expression of MHC class II genes. These include cell lines established from patients affected with MHC class II deficiency and experimentally generated mutant cell lines. Group D, in contrast to the other groups, was for a long time represented only by the 6.1.6 mutant cell line. The gene responsible for the defect in this group, RFXAP , recently was cloned and found to be mutated in the 6.1.6 cell line and in three patients. Here we report fusion experiments in several new HLA class II-deficient patients, completing the classification of the majority of known patients into the four complementation groups. Patients from five unrelated families were classified in complementation group D, while nine others fall into complementation groups A and B. None of the patients defined a new complementation group. Full correction of MHC class II expression was obtained in cells from patients belonging to group D by transfection with the RFXAP cDNA. The RFXAP coding region was found to be mutated in all patients. Mutations were found to be recurrent since only three different mutations have been found in the eight unrelated families reported to date.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1997

Mutation of RFXAP, a regulator of MHC class II genes, in primary MHC class II deficiency.

BACKGROUND: Major-histocompatibility-complex (MHC) class II deficiency is an autosomal recessive primary immunodeficiency disease in which MHC class II molecules are absent. It is a genetically heterogeneous disease of gene regulation resulting from defects in several transactivating genes that regulate the expression of MHC class II genes. The mutations responsible for MHC class II deficiency are classified according to complementation group (a group in which the phenotype remains uncorrected in pairwise fusions of cells). There are three known complementation groups (A, B, and C). METHODS: To elucidate the genetic defect in patients with MHC class II deficiency that was not classified genetically, we performed direct complementation assays with the three genes known to regulate the expression of MHC class II genes, CIITA, RFX5, and RFXAP, and the relevant mutations were identified in each patient. RESULTS: Mutations in the RFXAP gene were found in three patients from unrelated families, and the resulting defect was classified as belonging to a novel complementation group (D). Transfection with the wild-type RFXAP gene restored the expression of MHC class II molecules in the patients' cells. CONCLUSIONS: Mutations in a novel MHC class II transactivating factor, RFXAP, can cause MHC class II deficiency. These mutations abolish the expression of MHC class II genes and lead to the same clinical picture of immunodeficiency as in patients with mutations in the other two MHC class II regulatory genes.

Cell Line↗
PubMed1997

Barraquer-Simons syndrome (with sensorineural deafness): a contribution to the differential diagnosis of lipodystrophy syndromes.

Among the lipodystrophies, the Barraquer-Simons syndrome is a rare condition. We describe a 27-year-old woman with progressive loss of subcutaneous fat after 15 years first affecting the face and spreading to the upper part of the body. She also suffered from deafness and had marked changes in cranial MRI. We discuss possible differential diagnosis such as the Cockayne, SHORT and Berardinelli-Seip syndrome.

Adult↗
PubMed1997

RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency.

Major Histocompatibility Complex class II (MHC-II) deficiency is a disease of gene regulation that provides a unique opportunity for the genetic dissection of the molecular mechanisms controlling transcription of MHC-II genes. Cell lines from MHC-II deficiency patients have been assigned to three complementation groups (A, B and C) believed to reflect the existence of distinct essential MHC-II regulatory genes. Groups B and C, as well as an in vitro generated regulatory mutant representing a fourth group (D), are characterized by a specific defect in the binding activity of RFX, a multimeric DNA binding complex that is essential for activation of MHC-II promoters. RFX5, a subunit of RFX, was recently shown to be mutated in group C. We have now isolated a novel gene, RFXAP (RFX Associated Protein), that encodes a second subunit of the RFX complex. RFXAP is mutated in the 6.1.6 cell line (group D), as well as in an MHC-II deficiency patient (DA). This establishes that group D is indeed a fourth MHC-II deficiency complementation group. Complementation of the 6.1.6 and DA cell lines by transfection with RFXAP fully restores expression of all endogenous MHC-II genes in vivo, demonstrating that RFXAP is a novel essential MHC-II regulatory gene.

Amino Acid Sequence↗
PubMed1997

Analysis of mutations and chromosomal localisation of the gene encoding RFX5, a novel transcription factor affected in major histocompatibility complex class II deficiency.

MHC class II deficiency is a severe primary immunodeficiency characterised by the absence of major histocompatibility complex class II (MHC-II) gene expression. It is genetically heterogeneous and can result from defects in at least four different trans-acting regulatory genes required for transcription of MHC-II genes. One of these genes has recently been shown to encode a novel DNA binding protein called RFX5, which is one subunit of a heteromeric protein complex (RFX) that binds to the promoters of MHC-II genes. We have characterised the mutations in all four patients known to harbour a defect in the RFX5 gene and have mapped this new human disease gene to chromosome 1 band q21, a region frequently exhibiting chromosomal aberrations in a variety of preneoplastic and neoplastic diseases.

Chromosome Mapping↗
PubMed1997

Dynamic contrast-enhanced T2*-weighted MRI in patients with cerebrovascular disease.

Our purpose was to investigate the potential of dynamic susceptibility contrast-enhanced MRI in assessing regional haemodynamics in patients with cerebrovascular disease. T2*-weighted FLASH sequences were performed on a control group of 10 healthy subjects, 13 patients with unilateral stenosis or occlusion of the internal carotid artery and 6 patients with acute onset of neurological symptoms, the observed signal intensities being converted into concentration-time curves. A gamma-variate function was fitted to the measured concentration-time curves to eliminate effects of tracer recirculation. In each patient the two cerebral hemispheres were compared and the difference between the mean transit times and the percental change of the regional cerebral blood volume, calculated for each side. Patients with haemodynamically significant unilateral carotid obstruction can be divided into two subgroups: those with good and those with poor collateral supply. Patients with good collateral supply had a slight but not statistically significant increase in mean transit time and cerebral blood volume on the diseased side, whereas those with poor collaterals had a significant increase compared with the control group. In patients with acute onset of neurological symptoms perfusion maps clearly demonstrated the disturbed perfusion at a time when T2-weighted images were still normal. Perfusion imaging is a reliable and noninvasive method of assessing changes in cerebral perfusion in patients with unilateral carotid stenosis. This MR technique permits monitoring of haemodynamic changes during therapy and thus may become an alternative to SPECT and PET scanning. In patients with acute occlusion of a cerebral artery, perfusion imaging reveals the entire, perfusion deficit before conventional MRI and thus allows early intervention.

Acute Disease↗
PubMed1997

MHC class II deficiency: definition of a new complementation group.

MHC class II deficiency is a severe primary immunodeficiency characterized by the absence of Major Histocompatibility Complex class II gene expression. It is genetically heterogenous and can result from defects in several different transacting regulatory factors required for transcription of MHC class II genes. Cell lines from MHC class II deficiency patients have been assigned to three complementation groups (A, B, C). An in vitro generated cell line (6.1.6) was reported to be the sole representative of a fourth group (group D). The molecular defect in 6.1.6 resides in the recently cloned RFXAP gene. Direct complementation experiments and mutation analysis were performed with cell lines from several MHC class II deficiency patients in which the affected gene had not been identified. These experiments have allowed us to define a previously unrecognized MHC class II deficiency complementation group containing patients having mutations in the RFXAP gene.

Animals↗
PubMed1997

[Diffusion-weighted magnetic resonance tomography: a highly promising MR technic for the early recognition of cerebral ischemia].

PURPOSE: The aim of this study was to show the temporal and spatial evolution of ischaemia over time using diffusion-weighted magnetic resonance imaging, and to correlate the extent of ischaemia with the postmortem infarct size after 24 hours. MATERIAL AND METHODS: In 8 rats focal cerebral ischaemia was induced by intravascular occlusion of the middle cerebral artery. The evolution of the ischaemic lesion was examined over 180 min with an experimental MR scanner. RESULTS: Diffusion-weighted magnetic resonance imaging displayed a hyperintense area in the lateral part of the putamen as early as 5 min after the onset of ischaemia. The mean volume of ischaemia on diffusion mapping after 5 min was 62.5 +/- 12.9 microliters and increased to 224.4 +/- 48.5 microliters after 180 min. This correlated well with the corrected infarct volume at postmortem examination (194.0 +/- 23.1 microliters, r = 0.72, p < 0.05) using the TTC staining. CONCLUSION: Diffusion-weighted magnetic resonance imaging is a reliable tool in the early diagnosis of cerebral ischaemia. Due to the non-invasiveness this method can be used for therapy monitoring and might help to develop new therapeutic strategies.

Animals↗
PubMed1997

[Diffusion-weighted MR tomography in focal cerebral ischemia: possibilities offered by a 1.0 Tesla clinical device].

PURPOSE: To develop and to implement a fast, highly diffusion-weighted MR-sequence on a conventional 1 T MR scanner and to examine this sequence as to its capability of characterising tissue damage due to focal cerebral ischaemia. METHODS: Within a CE-FAST-sequence diffusion gradients were inserted in all gradient directions. By phantom measurements the maximal diffusion weighting was determined for different T1 and T2 values and flip angles. The optimised sequence was used for monitoring the diffusion of focal cerebral ischaemia in 14 rats following endovascular occlusion of the middle cerebral artery. RESULTS: The ischaemic lesion could be easily visualised as a bright area in the images with high diffusion weighting. The mean relative decrease of the diffusion coefficient in the ischaemic brain parenchyma was 29%. The diffusion coefficient, decreased significantly with increasing occlusion time. CONCLUSION: Our study suggests that the installed sequence is capable of producing highly diffusion weighted images without requiring a special gradient system. The sequence is potentially useful for monitoring cerebral ischaemia on the basis of calculating the change of the diffusion coefficient.

Animals↗
PubMed1997

[Studies on contrast medium dosage in perfusion-weighted MR imaging].

PURPOSE: In this study we investigated, whether increasing the dosage of a paramagnetic contrast agent results in a stronger signal decrease in T2*-weighted perfusion sequences and therefore more meaningful parameter maps. MATERIAL AND METHODS: In a prospective study bolus injection of gadolinium-DTPA was performed at dosages of 0.1, 0.2, and 0.3 mmol/kg body weight (BW) in 10 patients each. Before, during and after bolus injection 40 T2*-weighted images of a reference brain slice were acquired within 65.6 seconds on a 1.0 T clinical scanner and perfusion parameters were calculated. RESULTS: Due to the limited signal decrease during bolus passage and the resulting low signal-difference-to-noise ratio (delta S/N) no reliable differentiation of gray and white matter was possible at a contrast agent dosage of 0.1 mmol/kg BW. Only at higher dosages, both, signal decrease and delta S/N were strong enough to allow differentiation of gray and white matter and to yield reliable parameter maps. CONCLUSION: For meaningful MR perfusion imaging at 1.0 T and with the given sequence a contrast agent dosage of at least 0.2 mmol/kg BW is necessary, if a 0.5-molar contrast agent is used.

Adult↗
PubMed1997

Bolus injection of MR contrast agents: hemodynamic effects evaluated by intracerebral laser Doppler flowmetry in rats.

PURPOSE: To determine the effects on arterial blood pressure and cerebral blood flow of intravenous bolus injection of three MR contrast agents: gadopentetate dimeglumine, polylysine-Gd-DTPA, and superparamagnetic iron particles (SPIO). METHODS: A single-fiber laser Doppler flowmetry probe was placed intracerebrally in 56 anesthetized rats. Cerebral blood flow and mean arterial blood pressure were measured before (baseline), during, and up to 30 minutes after intravenous bolus administration of the three contrast agents: 0.1 mmol/kg and 0.3 mmol/kg gadopentetate dimeglumine (n = 18 per group), 0.3 mmol/kg polylysine-Gd-DTPA (n = 10), and 0.03 mmol/kg SPIO (n = 10). RESULTS: Neither the higher nor lower dose of gadopentetate dimeglumine had any statistically significant effect on cerebral blood flow, and there was no change in blood pressure during administration of either dose of gadopentetate dimeglumine. Administration of polylysine-Gd-DTPA caused a transient drop in blood pressure in two animals, marked in one (decrease to 21% of baseline values) and mild in the other (84% of baseline). After administration of SPIO, a significant decrease in blood pressure occurred in one animal (41% of baseline). Despite this decrease in mean arterial blood pressure, there were no statistically significant changes in cerebral blood flow after administration of polylysine-Gd-DTPA or SPIO. CONCLUSION: Our results suggest that bolus injection of these contrast agents at clinically relevant doses causes no significant alteration in cerebral blood flow. We conclude that gadopentetate dimeglumine is well suited for cerebral MR perfusion imaging without inherent influence on cerebral blood flow and that the same is probably true for polylysine-Gd-DTPA and SPIO.

Animals↗
PubMed1996

Locations of human and mouse genes encoding the RFX1 and RFX2 transcription factor proteins.

RFX transcription factors constitute a highly conserved family of site-specific DNA binding proteins involved in the expression of a variety of cellular and viral genes, including major histocompatibility complex class II genes and genes in human hepatitis B virus. Five members of the RFX gene family have been isolated from human and mouse, and all share a highly characteristic DNA binding domain that is distinct from other known DNA binding motifs. The human RFX1 and RFX2 genes have been assigned by in situ hybridization to chromosome 19p13.1 and 19p13.3, respectively. In this paper, we present data that localize RFX1 and RFX2 precisely within the detailed physical map of human chromosome 19 and genetic data that assign Rfx1 and Rfx2 to homologous regions of mouse chromosomes 8 and 17, respectively. These data define the established relationships between these homologous mouse and human regions in further detail and provide new tools for linking cloned genes to phenotypes in both species.

Animals↗
PubMed1996

RFX proteins, a novel family of DNA binding proteins conserved in the eukaryotic kingdom.

Until recently, the RFX family of DNA binding proteins consisted exclusively of four mammalian members (RFX1-RFX4) characterized by a novel highly conserved DNA binding domain. Strong conservation of this DNA binding domain precluded a precise definition of the motif required for DNA binding. In addition, the biological systems in which these RFX proteins are implicated remained obscure. The recent identification of four new RFX genes has now shed light on the evolutionary conservation of the RFX family, contributed greatly to a detailed characterization of the RFX DNA binding motif, and provided clear evidence for the function of some of the RFX proteins. RFX proteins have been conserved throughout evolution in a wide variety of species, including Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans, mouse and man. The characteristic RFX DNA binding motif has been recruited into otherwise very divergent regulatory factors functioning in a diverse spectrum of unrelated systems, including regulation of the mitotic cell cycle in fission yeast, the control of the immune response in mammals, and infection by human hepatitis B virus.

Amino Acid Sequence↗
PubMed1996

[High dosage administration of paramagnetic contrast media in diagnosis of focal brain lesions].

In analogy with high-dose contrast-enhanced CT, there have been a few studies during recent years that have dealt with high-dose paramagnetic contrast dyes in MRI. One reason for these studies was the development of new and low-osmolar contrast agents in the MR field. Depending on the clinical problem, a high-dose contrast study in MRI is rarely indicated: (1) in metastatic disease, MR imaging with high-dose contrast material is indicated when the standard dose study is negative or only shows a solitary cerebral lesion or a number of lesions just suitable for radiosurgery; (2) in patients with malignant glioma the high-dose study allows better definition of the tumor margins. If a radical surgical approach is planned, the diagnostic potential should be fully used; if only a biopsy or subtotal debulking is planned, a standard dose study is enough. (3) in patients with MS, a high-dose study is only recommended within therapeutic trials in which the number of active plaques is a primary variable.

Brain↗