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W Reith

Publications and source records attributed to W Reith.

119 records · Page 7Linked to original sources
PubMed1989

Cloning of the major histocompatibility complex class II promoter binding protein affected in a hereditary defect in class II gene regulation.

The regulation of major histocompatibility complex class II gene expression is directly involved in the control of normal and abnormal immune responses. In humans, HLA-DR, -DQ, and -DP class II heterodimers are encoded by a family of alpha- and beta-chain genes clustered in the major histocompatibility complex. Their expression is developmentally controlled and normally restricted to certain cell types. This control is mediated by cis-acting sequences in class II promoters and by trans-acting regulatory factors. Several nuclear proteins bind to class II promoter sequences. In a form of hereditary immunodeficiency characterized by a defect in a trans-acting regulatory factor controlling class II gene transcription, we have observed that one of these nuclear factors (RF-X) does not bind to its target sequence (the class II X box). A cDNA encoding RF-X was isolated by screening a phage expression library with an X-box binding-site probe. The recombinant protein has the binding specificity of RF-X, including a characteristic gradient of affinity for the X boxes of HLA-DR, -DP, and -DQ promoters. RF-X mRNA is present in the regulatory mutants, indicating a defect in the synthesis of a functional form of the RF-X protein.

Base Sequence↗
PubMed1989

Inherited immunodeficiency with a defect in a major histocompatibility complex class II promoter-binding protein differs in the chromatin structure of the HLA-DRA gene.

A defect in a trans-regulatory factor which controls major histocompatibility complex class II gene expression is responsible for an inherited form of immunodeficiency with a lack of expression of human leukocyte antigen (HLA) class II antigens. We have recently described and cloned an HLA class II promoter DNA-binding protein, RF-X, present in normal B cells and absent in these class II-deficient regulatory mutants. Here we report that these in vitro results correlate with a specific change in the chromatin structure of the class II promoter: two prominent DNase I-hypersensitive sites were identified in the promoter of the HLA-DRA gene in normal B lymphocytes and found to be absent in the class II-deficient mutant cells. The same two prominent DNase I-hypersensitive sites were observed in normal fibroblastic cells induced by gamma interferon to express class II genes. Interestingly, they were also observed in the uninduced class II-negative fibroblastic cells, which have also been shown to have a normal RF-X binding pattern. We conclude that the two DNase I-hypersensitive sites in the HLA-DRA promoter reflect features in chromatin structure which correlate with the binding of the trans-acting factor RF-X and which are necessary but not sufficient for the expression of class II genes.

B-Lymphocytes↗
PubMed1988

Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X.

The expression of MHC class II genes is tightly regulated. One form of congenital severe combined immunodeficiency (SCID) is characterized by a regulatory defect that precludes expression of HLA class II genes. B lymphocyte cell lines from such SCID patients provide a tool for identifying putative regulatory proteins that bind to class II gene promoters. We have identified three proteins binding to specific segments of the HLA-DRA promoter, two of which interact to form the predominant DNA-protein complex observed. One of these proteins, defined as an X box binding protein (RF-X), is specifically missing in cells from class II deficient SCID patients. We propose that the molecular defect in this congenital HLA class II regulatory deficiency is a lack of RF-X and that this factor plays an important role in the normal regulation of MHC class II gene expression.

B-Lymphocytes↗
PubMed1984

Identification of Xenopus laevis mRNAs with homology to repetitive sequences.

Hybrid selection translation experiments have been carried out with genomic and cDNA relatives of two repetitive sequence families. On the basis of the in vitro translation products detected, it was found that transcripts complementary to these repeats are linked to several different mature mRNAs in stage 40 embryos of Xenopus laevis. One repeat hybridizes to mRNAs that direct the synthesis of 17 proteins. The second is present on mRNAs coding for 3 proteins. By estimating the abundance of these proteins among the translation products of total embryonic mRNA, it is inferred that all of the repeat bearing mRNAs are rare, less than one in 20,000 mRNA molecules.

Animals↗
PubMed1983

Structural analysis of repetitive sequence elements transcribed in early development of Xenopus laevis.

A cDNA library prepared from mRNA of Xenopus laevis embryos was screened with a genomic DNA fragment containing various transcribed repetitive sequence elements. Comparison of the nucleotide sequence of two isolated cDNAs and their genomic relatives allows one to define two transcribed repetitive sequence elements. One of them belongs to a highly reiterated family and consists of a tandem array of homologous subunits of 77-80 bp. The other is reiterated approximately 2200 times, has a size of 260 bp and displays a conserved region of 135 bp. The data are consistent with the presence of repetitive sequence transcripts in the 3' part of mRNA molecules.

Animals↗
PubMedDate not supplied

Perfusion-weighted MRI using gadobutrol as a contrast agent in a rat stroke model.

The purpose of this study was to examine the new nonionic contrast agent gadobutrol in MR perfusion-weighted imaging, including the influence of different concentrations and dosages of the agent on the sensitivity to perfusion alterations. Sixteen rats were examined within 35 to 105 minutes after endovascular occlusion of the middle cerebral artery. A fast T2*-weighted fast low-angle shot (FLASH) sequence was used to acquire four images before and 16 images after bolus injection of .1, .2, .3, and .4 mmol/kg gadobutrol as .5 molar and 1.0 molar formulation. From user-defined regions, we obtained the maximum signal decrease, the relative regional cerebral blood volume, and the bolus delay. Contrast between ischemic and nonischemic regions during bolus passage increased with dose and concentration of the contrast agent. For low doses (.1 and .2 mmol/kg), the ischemic lesion could not or could barely be discerned. For higher doses (.3 and .4 mmol/kg), administration of the 1 molar contrast agent yielded a better contrast between ischemic and nonischemic tissue. Our results suggest that administration of gadobutrol at higher dosage and higher concentration increases sensitivity to perfusion alterations. These results are potentially useful for perfusion-weighted imaging of the human brain, because the volume of contrast agent will be reduced if a solution with higher concentration is used. When using contrast agents in higher concentrations for human examinations, a significant signal decrease may be achieved also with the low doses (.1-.15 mmol/kg).

Animals↗