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Biomedical subjects

S Brenner

Publications and source records attributed to S Brenner.

At least 73 records · Page 4Linked to original sources
PubMed2000

Catecholamines induce IL-10 release in patients suffering from acute myocardial infarction by transactivating its promoter in monocytic but not in T-cells.

The anti-inflammatory cytokine IL-10 is up-regulated in response to TNF-alpha suggesting a control mechanism of inflammation. In addition, we recently found systemic IL-10 release in response to acute stress reactions in the absence of any systemic inflammation. In vitro and in vivo studies in experimental models suggest that catecholamines induce IL-10 release via a cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) dependent pathway. Here we studied patients for plasma IL-10 after acute myocardial infarction, a very stressful event without significant signs of systemic inflammation. In fact, the activation of the sympathetic system initiated by cardiac infarction was accompanied by a temporary systemic release of IL-10. Catecholamine induced IL-10 may be released by different cells. Recently, we demonstrated that catecholamines directly stimulate the IL-10 promoter/enhancer via a cAMP/PKA pathway in monocytic cells. A cAMP responsive element (CRE) was identified as major target. Here we show that there is no influence of catecholamines on the IL-10 promoter activity in T-cells. In contrast to monocytic cells, in T-cells cAMP-induced PKA-dependent phosphorylation of the CRE-binding protein 1 (CREB-1) seems to play a marginal role in IL-10 induction, which was reflected by a low cAMP-dependent IL-10-promoter/enhancer stimulation in reporter gene assays. Thus, catecholamines are directly involved in the regulation of IL-10 expression in monocytic but not in T-cells after acute stressful conditions.

Acute Disease↗
PubMed1999

Theoretical biology in the third millennium.

During the 20th century our understanding of genetics and the processes of gene expression have undergone revolutionary change. Improved technology has identified the components of the living cell, and knowledge of the genetic code allows us to visualize the pathway from genotype to phenotype. We can now sequence entire genes, and improved cloning techniques enable us to transfer genes between organisms, giving a better understanding of their function. Due to the improved power of analytical tools databases of sequence information are growing at an exponential rate. Soon complete sequences of genomes and the three-dimensional structure of all proteins may be known. The question we face in the new millennium is how to apply this data in a meaningful way. Since the genes carry the specification of an organism, and because they also record evolutionary changes, we need to design a theoretical framework that can take account of the flow of information through biological systems.

Animals↗
PubMed1999

A genetic screen to identify sequences that mediate protein oligomerization in Escherichia coli.

Many proteins assemble as oligomeric complexes and in several cases a distinct domain mediates the interaction between the subunits. The identification of new oligomerization modules is relevant to comprehend both the architecture and the evolution of protein sequences and also for protein engineering applications. Using the bacteriophage lambda repressor dimerization assay, we searched Escherichia coli genomic libraries for sequences able to mediate protein oligomerization in vivo. We identified short peptides that can substitute very effectively the dimerizing domain of the repressor. Most of these peptides belong to open reading frames that are normally not expressed in the bacterial cell.

Amino Acid Sequence↗
PubMed1999

Moron peer review.

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National Institutes of Health (U.S.)↗
PubMed1999

Molecular cloning of EDG-3 and N-Shc genes from the puffer fish, Fugu rubripes, and conservation of synteny with the human genome.

EDG-3 is a receptor for sphingosine-1-phosphate mapped on human chromosome 9q22.1-q22.2. We used the compact Fugu genome for its linkage analysis. The Fugu EDG-3 was composed of one intron and two exons, encoding a 384 amino acid protein that has 56.9% homology with the human EDG-3. Approximately 3 kb apart, a neuronal Shc (N-Shc) gene was identified. It spans 7 kb containing 12 coding exons, and has an overall 53.4% similarity with the human protein. We mapped the human N-Shc gene to chromosome 9q21.3-q22.2. This is the first report of the genomic structure and the linkage of these two genes conserved between Fugu and human.

Amino Acid Sequence↗
PubMed1999

Late changes in spliceosomal introns define clades in vertebrate evolution.

The evolutionary origin of spliceosomal introns has been the subject of much controversy. Introns are proposed to have been both lost and gained during evolution. If the gain or loss of introns are unique events in evolution, they can serve as markers for phylogenetic analysis. We have made an extensive survey of the phylogenetic distribution of seven spliceosomal introns that are present in Fugu genes, but not in their mammalian homologues; we show that these introns were acquired by actinopterygian (ray-finned) fishes at various stages of evolution. We have also investigated the intron pattern of the rhodopsin gene in fishes, and show that the four introns found in the ancestral chordate rhodopsin gene were simultaneously lost in a common ancestor of ray-finned fishes. These changes in introns serve as excellent markers for phylogenetic analysis because they reliably define clades. Our intron-based cladogram establishes the difficult-to-ascertain phylogenetic relationships of some ray-finned fishes. For example, it shows that bichirs (Polypterus) are the sister group of all other extant ray-finned fishes.

Amino Acid Sequence↗
PubMed1999

Isolation and characterisation of the retinoic acid receptor-alpha gene in the Japanese pufferfish, F. rubripes.

Nuclear hormone receptors (NRs) are ligand-inducible transcription factors that mediate critical functions in many species. The majority of novel NRs have hitherto been cloned from cDNA libraries by virtue of their homology to previously identified receptors. In this study, we validate a genomic DNA-based approach to isolating NRs by cloning the retinoic acid receptor-alpha (RARalpha) gene from the genome of the Japanese pufferfish, Fugu rubripes. The fRARalpha gene is more compact than its human and murine counterparts and demonstrates a highly conserved genomic organisation and amino acid sequence, generating two isoforms (fRARalpha1 and fRARalpha2) with divergent aminoterminal domains. In addition, a conserved regulatory element containing a retinoic acid response element was identified upstream of the fRARalpha2-specific exon, implying that retinoid induction of this isoform is evolutionarily conserved and critical to its function in vivo. We propose two uses for the Fugu genome in the study of NRs: the isolation of novel NRs that exhibit restricted spatio-temporal expression from genomic DNA and the identification of evolutionarily conserved promoter or intragenic regulatory DNA elements.

Amino Acid Sequence↗
PubMed1999

O sole mio!

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Journal Article↗
PubMed1999

The march of thyme.

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Genetic Engineering↗
PubMed1999

Distinct cis-essential modules direct the time-space pattern of the Pax6 gene activity.

Pax6 is a regulatory gene with restricted expression and essential functions in the developing eye and pancreas and distinct domains of the CNS. In this study we report the identification of three conserved transcription start sites (P0, P1, alpha) in the murine Pax6 locus. Furthermore, using transgenic mouse technology we localized independent cis-regulatory elements controlling the tissue-specific expression of Pax6. Specifically, a 107-bp enhancer and a 1.1-kb sequence within the 4.6-kb untranslated region upstream of exon 0 are required to mediate Pax6 expression in the lens, cornea, lacrimal gland, conjunctiva, or pancreas, respectively. Another 530-bp enhancer fragment located downstream of the Pax6 translational start site is required for expression in the neural retina, the pigment layer of the retina, and the iris. Finally, a 5-kb fragment located between the promoters P0 and P1 can mediate expression into the dorsal telencephalon, the hindbrain, and the spinal cord. The identified Pax6/cis-essential elements are highly conserved in pufferfish, mouse, and human DNA and contain binding sites for several transcription factors indicative of the cascade of control events. Corresponding regulatory elements from pufferfish are able to mimic the reporter expression in transgenic mice. Thus, the results indicate a structural and functional conservation of the Pax6 regulatory elements in the vertebrate genome.

Animals↗
PubMed1999

Iatrogenic cutaneous injuries in the neonate.

BACKGROUND: Iatrogenic cutaneous injuries of the neonate have decreased in number in the last 30 years because of changes in the medical procedures during the prenatal, perinatal, and postnatal periods. OBSERVATIONS: The emergence of such cutaneous injuries derived from the use of instruments, blunt and sharp, from manual manipulations, from medications, and from hesitation or abstaining from intervention. CONCLUSION: The dermatologist, unfamiliar with handling of neonates in the nursery, should be capable of recognizing and dealing with these phenomena when encountered in the acute stage or with their residue.

Humans↗
PubMed1999

Short-range linkage relationships, genomic organisation and sequence comparisons of a cluster of five HSP70 genes in Fugu rubripes.

Twelve cosmids containing sequences resembling genes encoding members of the 70-kDa heat-shock protein family, HSP70. have been isolated from Fugu rubripes. They can be broadly divided into three groups of overlapping cosmids. Restriction analysis and sequencing of one set of five cosmids have revealed five intronless Fugu HSP70 genes spanning 42 kb, arranged in a combined head-to-head, tail-to-tail and head-to-tail orientation. The levels of DNA and amino acid identity are very high with respect to one another, and are most similar to HSP70 sequences linked to the major histocompatibility complex (MHC) region in other species. Putative heat-shock consensus elements are identified. Non-HSP70 sequences with homology to known genes have been found physically linked to this Fugu HSP70 cluster: the Drosophila melanogaster SOL gene, the Drosophila melanogaster nemo gene, the Caenorhabditis elegans T17E9.1 gene and the sequence encoding the serine protease domain. The linkage relationships described here so far bear no resemblance to those of HSP70 in other organisms. Convergence of mammalian HSP70 and MHC class I and II loci probably occurred after fish had diverged.

Amino Acid Sequence↗
PubMed1999

Unusual eruption as a presenting symptom of cat scratch disease.

Cat scratch disease (CSD) is a common infectious cause of subacute regional lymphadenopathy. Bartonella henselae is the principal etiologic agent. About 10% of CSD patients experience atypical manifestations, including rashes. The most common cutaneous manifestation of CSD is a papule at the inoculation site. We report a case of CSD presenting with an eruption on the upper trunk, reminiscent of Sweet's syndrome, accompanied by lymphadenopathy, arthralgia, and fever. Response to systemic corticosteroids was remarkable. Histopathologic findings refuted the diagnosis of Sweet's syndrome. Identification of anti-B henselae antibodies and B henselae DNA in the affected lymph node confirmed the diagnosis of CSD. This is a first report of extensive papuloedematous eruption as a cutaneous manifestation of CSD. Accurate diagnosis is possible due to the availability of serological tests and DNA amplification techniques.

Adult↗