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D W Burt

Publications and source records attributed to D W Burt.

86 records · Page 5Linked to original sources
PubMed1988

Increased tumor necrosis factor and IL-1 beta gene expression in the kidneys of mice with lupus nephritis.

Because TNF and IL-1 can initiate immunologic and inflammatory events alone or synergistically, a local increase in the levels of one or both of these cytokines in vivo may cause irreparable tissue damage. The purpose of this study was to evaluate local TNF and IL-1 beta gene expression in vivo in the kidneys of MRL-Ipr mice with autoimmune lupus nephritis. TNF mRNA was detected in the renal cortex of MRL-Ipr mice but was not present in the cortex of normal congenic MRL-++ or C3H/FeJ mice. MRL-Ipr mice with lupus nephritis expressed higher amounts of TNF mRNA compared with MRL-Ipr mice prior to disease. In addition, freshly isolated, unstimulated glomeruli from MRL-Ipr mice with nephritis were found to secrete detectable levels of TNF, whereas glomeruli from MRL-++ mice did not. IL-1 beta mRNA, present in the renal cortex of C3H/FeJ, MRL-++, and young MRL-Ipr mice with normal kidneys, was also more abundantly expressed in MRL-Ipr mice with nephritis. Cultured macrophages from glomeruli of mice with nephritis were found to express TNF and IL-1 beta mRNA and product. These macrophages are prominent only in MRL-Ipr mice with renal disease and are the likely source of increased gene expression for both cytokines.

Animals↗
PubMed1988

Novel and enhanced IL-1 gene expression in autoimmune mice with lupus.

IL-1 is a pleiotropic factor encoded for by at least two genes, alpha and beta, and capable of eliciting a broad set of immunologic and inflammatory events. MRL/MP-lpr (MRL-lpr) mice are an appealing model for studies of renal injury inasmuch as disease in this strain is spontaneous, rapid, predictable, and regulated by the lpr gene. Infiltration of macrophages and the proliferation of the glomerular mesangial cells are prominent features of renal disease. Because both mesangial cells and macrophages can synthesize IL-1, the purpose of this study was to determine whether enhanced IL-1 gene expression is associated with lupus nephritis in the MRL-lpr mouse model. Glomerular macrophages, abundant in the kidneys of MRL-lpr mice but rarely present in the kidney of congenic MRL/MP-++(MRL-++) mice, were isolated and cultured and found to express a 10-fold increase in both IL-1 alpha and IL-1 beta mRNA transcripts as compared with MRL-++ and MRL-lpr mesangial cells. IL-1 alpha was not detected in the total RNA extracted from freshly excised kidney, whereas IL-1 beta transcripts were detected in both the renal cortex of MRL-lpr as well as MRL-++ animals. A previously undetected truncated 1200 nucleotide IL-1 beta transcript together with the conventional 1600 nucleotide IL-1 beta transcript was found in kidneys from MRL-lpr and was abundantly expressed in glomeruli of MRL-lpr mice with lupus nephritis. Isolated glomeruli from MRL-lpr mice with nephritis produce IL-1, whereas in normal glomeruli from MRL-++ and C3H/FeJ mice this cytokine was not detected. Glomerular macrophages and mesangial cells cultured from MRL-lpr mice with nephritis both secrete IL-1. These studies indicate that IL-1 beta gene expression and IL-1 protein are increased in the kidneys of autoimmune mice with lupus nephritis and is generated, at least in part, by glomerular macrophages. We speculate that an alteration in IL-1 beta gene expression may be responsible for causing a cascade of events leading to acute and chronic renal injury.

Animals↗
PubMed1988

Mapping of the human renin transcription start site: evidence for a single functional promoter.

The 5' flanking region of the human renin gene contains two putative promoter sequences (TATA boxes), named P1 and P2. These are located in positions -77 to -71 and -29 to -23 respectively, each followed by a possible translational start site (AUG). In order to identify whether these sequences are functional in the kidney, we employed the RNAse protection assay. Total RNA extracted from human kidney cortex was hybridized with labeled cRNA probes complementary to the 5' flanking region of the human renin gene. After digestion with RNAse, protected hybrids were identified by electrophoresis on polyacrylamide/urea gels and autoradiography. Results showed that only P2 is active in human kidney resulting in a single transcript. This suggests that human kidney renin is synthesized as a single preproform.

Humans↗
PubMed1988

Functional human renin promoter in transfected cells: evidence for cell-specific expression.

Expression of the human renin gene is regulated in a tissue-specific manner, but study of this regulation has been limited by a lack of suitable cell lines that simulate endogenous control. In order to characterize the regulation of renin gene expression, the 5' flanking region (892 base pairs) from the human renin gene was linked to the chloramphenicol acetyltransferase gene and was introduced into multiple human cell lines by calcium phosphate precipitation or electroporation methods to assess transcriptional control. The human renin promoter was active when transfected into cultured human choriocarcinoma cells (JEG-3) and rat vascular smooth muscle cells, but it was not active in many other cloned cell types. These results suggest that selective cell lines contain the specific trans-acting factors necessary for human renin gene expression, and support the concept of cell-specific expression of this gene.

Cell Differentiation↗
PubMed1988

Molecular biology of the renin-angiotensin system.

This paper reviews the molecular biology of the renin-angiotensin system. The renin gene structure is analyzed in detail, including an examination of the putative regulatory regions. The combined action of these regulatory sequences would result in the complex, tissue-specific expression and regulation observed in vivo. The expression of the tissue renin-angiotensin systems, which may have important physiological functions, is also described. In addition, the pathway of renin biosynthesis and secretion is reviewed. This includes speculation on the fate of circulating prorenin and the physiological role of multiple renin forms and secretory pathways. The molecular approaches described in this paper have greatly advanced our knowledge of the biology of the renin-angiotensin system. Future studies using these and other approaches should provide further insight into this complex system.

Angiotensin II↗
PubMed1985

Left subclavian artery trauma: in situ vs. rib interspace mobilization for primary anastomosis.

Fifteen autopsy dissections were performed to evaluate the anatomic relationships of the left subclavian artery and primary arterial anastomosis following trauma. The vessel was transected just beyond the origin of the thyrocervical trunk, and the maximal excisable overlapping segment was determined in situ and through the first and second interspaces. By passing the mobilized left axillary artery through the first intercostal space, up to 7.5 cm of a subclavian arterial segment could be resected and primary arterial repair accomplished. The use of the first interspace to gain additional length in primary repair of the left subclavian artery is suggested as an alternative to grafting.

Adult↗
PubMed1984

A retroviral provirus closely associated with the Ren-2 gene of DBA/2 mice.

We have determined the entire nucleotide sequence of an intra-cisternal A particle (IAP) genome, associated with the Ren-2 gene of DBA/2 mice. This genome (MIARN) displays features common to other IAP retroviral-like genomes. Long terminal repeats (LTRs) are approximately 430 base pairs (bp) in length and show typical retroviral U3-R-U5 organisation, though the R-region, at 120 bp, is much larger than the average IAP. This difference probably arose by the amplification of a pyrimidine-rich sequence, by a slippage-mispairing mechanism. Flanking the 5' LTR is a sequence complementary to a phenylalanine tRNA, strongly conserved in all rodent IAP genomes and probably required to prime the initiation of (-) strand synthesis. Flanking the 3' LTR, is a purine-rich sequence probably required for (+) strand synthesis. The tRNA binding site (TBS) is flanked by six tandem copies of a sequence homologous to the TBS. The relationship of the MIARN element to other IAP genomes and the significance of its association with the highly expressed Ren-2 is discussed.

Animals↗
PubMed1982

Molecular cloning of two distinct renin genes from the DBA/2 mouse.

We report the molecular cloning of cDNA copies of DBA/2 mouse submaxillary gland (SMG) renin mRNA, which were used to probe Southern transfers of mouse genomic DNA. The results suggested either that there is a single renin gene containing a large intron in that part of the gene corresponding to the probe, or that there are two distinct renin genes. We have shown that the latter is the case by cloning and isolating two similar but distinct renin genes from DBA/2 mouse DNA. Restriction maps of the regions containing the two renin genes are presented, together with nucleotide sequence data locating a complete exon coding for amino acids 268-315 of mouse SMG renin.

Animals↗
PubMed1982

Transcriptional termination sites in the b2 region of bacteriophage lambda that are unresponsive to antitermination.

A bacteriophage lambda cloning vector carrying the trp/lacW205 substitution is described. The vector facilitates the fusion in vitro of genetic control signals to the lacZ structural gene of Escherichia coli. This system was used to define transcriptional termination sites in the lambda b2 region. This region contains termination sites that are unresponsive to the lambda antiterminating proteins pQ and pN.

Bacteriophage lambda↗
PubMed1982

The cis-specificity of the Q-gene product of bacteriophage lambda.

A trp/lacW205 substitution, fused to the late region of bacteriophage lambda, provided a convenient assay for phage late gene expression in the presence or absence of lambda pQ. Comparison of lacZ expression from Q+ and Q- phages showed that late gene expression was markedly Q-dependent (263-fold difference). A cis/trans comparison of lambda pQ action showed a 180-fold difference in lacZ expression. The results suggest that pQ in only significantly active when supplied in cis to its site of action.

Bacteriophage lambda↗
PubMedDate not supplied

Genetic and physical mapping of the chicken IGF1 gene to chromosome 1 and conservation of synteny with other vertebrate genomes.

The chicken insulin-like growth factor 1 gene has been assigned to the short arm of chromosome 1 near the centromere by fluorescence in situ hybridization and genetic linkage analysis. Comparison of physical and genetic linkage maps locates the centromere between the IGF1 and GAPD loci. Comparison of the genetic maps of chicken and other vertebrates reveals a highly conserved syntenic group, including the GAPD-IGF1 loci.

Animals↗