Search PubMed⌕ Search

Biomedical subjects

S Brenner

Publications and source records attributed to S Brenner.

At least 145 records · Page 8Linked to original sources
PubMed1997

Recognition of pemphigus antigens in drug-induced pemphigus vulgaris and pemphigus foliaceus.

BACKGROUND: The clinical appearance and biologic behavior of drug-induced pemphigus depend on the type of inducing drug. OBJECTIVE: Our purpose was to investigate patients with drug-induced pemphigus vulgaris and pemphigus foliaceus antigens and compare results of studies to detect antibody reactivity in sera of these patients with the serology of patients with idiopathic pemphigus. METHODS: Ten patients with drug-induced pemphigus were studied. Antibody reactivity was determined against the pemphigus vulgaris antigen, desmoglein 3, and against desmoglein 1. RESULTS: The patient with pemphigus foliaceus and low levels of autoantibodies precipitated neither antigen. One patient with pemphigus vulgaris and high levels of antibody also failed to precipitate any specific antigen. Sera from eight patients with drug-induced pemphigus vulgaris had circulating autoantibodies directed to either the pemphigus vulgaris or pemphigus foliaceus antigen. Low levels of antibody in two of these eight patients precipitated only the pemphigus foliaceus antigen. High levels of antibody in five of the eight patients precipitated the pemphigus vulgaris antigen; two of these also reacted with the pemphigus foliaceus antigen. CONCLUSION: The autoantibody response was similar in both spontaneous and drug-related disease. A similar molecular mechanism in the two types of pemphigus is suggested.

Adult↗
PubMed1997

Organization of the Fugu rubripes Hox clusters: evidence for continuing evolution of vertebrate Hox complexes.

The clustered organization of Hox genes provides a powerful opportunity to examine gene gain and loss in evolution because physical linkage is a key diagnostic feature which allows homology to be established unambiguously. Furthermore, Hox genes play a key role in determination of axial and appendicular skeletal morphology and may be a key component of the evolution of diverse metazoan body forms. Despite suggestions that changes in Hox gene number played a role in evolution of metazoan body plans, there has been a general lack of evidence for such variation amongst gnathostomes (or indeed any vertebrate) and it has therefore been widely assumed that differential regulation may be the key element in all vertebrate Hox evolution. We have studied the Hox gene clusters of a teleost fish, Fugu rubripes, to test the possibility that Hox organization may have varied since the origin of jawed vertebrates. We have identified four Hox complexes in Fugu and found an unprecedented degree of variation when compared with tetrapod clusters. Our data show that: Fugu clusters are widely variant with respect to length; at least nine genes have been lost; there is a new group-2 paralogue; and pseudo-gene remnants of group-1 and group-3 paralogues were found in the Hoxc complex, when compared with the present mammalian clusters. We show that gene loss after duplication of the prototypical vertebrate Hox clusters is a key feature of both tetrapod and fish evolution.

Amino Acid Sequence↗
PubMed1997

Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains.

PKD1 is the major locus of the common genetic disorder autosomal dominant polycystic kidney disease (ADPKD). Analysis of the predicted protein sequence of the human PKD1 gene, polycystin, shows a large molecule with a unique arrangement of extracellular domains and multiple putative transmembrane regions. The precise function of polycystin remains unclear with a paucity of mutations to define key structural and functional domains. To refine the structure of this protein we have cloned the genomic region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA and has greater complexity with 54 exons compared with 46 in man. Comparative analysis of the predicted protein sequences shows a lower level of homology than in similar studies with identity of 40 and 59% similarity. However key structural motifs including leucine rich repeats (LRR), a C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A region of homology with the sea urchin REJ protein was also confirmed in Fugu but found to extend over 1000 amino acids. Several highly conserved intra- and extra-cellular regions, with no known sequence homologies, that are likely to be of functional importance were detected. The likely structure of the membrane associated region has been refined with similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels highlighted over part of this area. The overall protein structure has therefore been clarified and this comparative analysis derived structure will form the basis for the functional study of polycystin and its individual domains.

Amino Acid Sequence↗
PubMed1997

Histopathologic findings in drug-induced pemphigus.

Drug-induced pemphigus represents a diagnostic challenge, as usually no clinical feature differentiates it from its idiopathic counterpart. It was suggested recently that some histologic features may assist in diagnosing drug-associated diseases. The purpose of the study was to determine whether the histologic criteria suggested in the literature are specific enough to arouse suspicion of drug-induced pemphigus. Biopsy specimens of drug-induced and idiopathic pemphigus were reviewed by five dermatologists with no clinical data available about the patients. The sections were assessed to the presence of spongiosis with eosinophils, vacuolar degeneration, and the degree of acantholysis and cleavage level. Using the suggested criteria, the reviewers were unable to confirm a diagnosis of drug-induced pemphigus. It is advisable to consider drug etiology in every case of newly diagnosed pemphigus based on clinical criteria an detailed drug consumption history, as histologic features do not differentiate between drug-associated and idiopathic disease.

Acantholysis↗
PubMed1997

Protein folds in the all-beta and all-alpha classes.

Analysis of the structures in the Protein Databank, released in June 1996, shows that the number of different protein folds, i.e. the number of different arrangements of major secondary structures and/or chain topologies, is 327. Of these folds, approximately 25% belong to the all-alpha class, 20% belong to the all-beta class, 30% belong to the alpha/beta class, and 25% belong to the alpha + beta class. We describe the types of folds now known for the all-beta and all-alpha classes, emphasizing those that have been discovered recently. Detailed theories for the physical determinants of the structures of most of these folds now exist, and these are reviewed.

Databases, Factual↗
PubMed1997

Diclofenac: a new trigger of pemphigus vulgaris?

Many drugs have been shown to induce pemphigus, including thiol and nonthiol drugs. We present a case of pemphigus vulgaris where a nonsteroidal anti-inflammatory medication, diclofenac in suppositories and topical gel preparations, is suspected of having triggered the disease. The temporal relationship between drug and outbreak of disease together with the positive migration inhibition factor test to diclofenac point to the possible involvement of this drug in triggering pemphigus vulgaris.

Administration, Cutaneous↗
PubMed1997

Paraneoplastic subacute cutaneous lupus erythematosus: report of a case associated with cancer of the lung.

A case of subacute cutaneous lupus erythematosus (SCLE) associated with lung carcinoma is presented. A review of the literature revealed only 5 other cases of SCLE associated with internal malignancy. The tumor in the described case most probably developed before the appearance of the eruption. Cancer chemotherapy was followed by shrinkage of tumor mass and regression of the skin lesions. The sequence of these events corresponds to the definition of paraneoplastic dermatoses.

Antibiotics, Antineoplastic↗
PubMed1997

Genomic structure and sequence analysis of the valyl-tRNA synthetase gene of the Japanese pufferfish, Fugu rubripes.

The genomic sequence and exon-intron organisation of the valyl-tRNA synthetase gene in the Japanese pufferfish, Fugu rubripes, have been determined. This single-copy Fugu gene spans 8.5 kb, about 2.5 times smaller than that in man (21 kb). It contains 29 exons, with the largest intron being 1008 bp. The predicted polypeptide consists of 1217 amino acids, with a molecular weight of 138 kD and an isoelectric point of 7.27. It shares 40% identity in the overlapping region with its homolog in bacteria, 47% with yeast, and 67% with man. The Fugu gene has an additional N-terminal sequence which shows strong similarity to elongation factory-1gamma, a feature it shares only with the human sequence, but not with any other lower eukaryote or prokaryote studied so far. This N-terminal segment is encoded in the first six exons, suggesting their capture by a translocation through introns. Indeed, the acquisition of extra domains to perform related functions in RNA splicing and translation of polypeptides has already been observed in other aminoacyl-tRNA synthetases. Two cDNA sequences of human valyl-tRNA synthetase have been published, with discrepancies between them. Aided by comparisons with the Fugu gene, three of these discrepancies have been resolved, involving the elucidation of the sequence and positions of two introns. This compact vertebrate genome has demonstrated its value as a tool for the analysis of genes at the genomic level.

Amino Acid Sequence↗
PubMed1996

The tuberin (TSC2), autosomal dominant polycystic kidney disease (PKD1), and somatostatin type V receptor (SSTR5) genes form a synteny group in the Fugu genome.

The tuberous sclerosis 2 (TSC2) and polycystic kidney disease 1 (PKD1) genes are adjacent on human chromosome 16p13.3 and form part of a conserved synteny group with mouse chromosome 17. We have determined that the PKD1 gene is evolutionarily conserved, single copy, and linked to TSC2 in the Fugu genome. A short cosmid contig has been identified containing both genes based on hybridization, exon trapping, and random sequence data. In addition sequences homologous to the somatostatin type V receptor (SSTR5) were identified 5' to PKD1, defining a larger syntenic region, as this gene has also been mapped to human chromosome 16p13.3. As in mammalian genomes, the Fugu TSC2 and PKD1 genes are adjacent in a tail-to-tail orientation.

Animals↗
PubMed1996

How do I rate?

Explore the source record for details and available documents.

Journal Article↗
PubMed1996

Molecular cloning of the novel human G protein-coupled receptor (GPCR) gene mapped on chromosome 9.

A novel human GPCR gene was cloned by PCR with degenerate primers designed from cannabinoid type 1 receptor (CB1) sequences and a full-length clone was isolated by screening of a human genomic DNA library. This gene, termed EDG-3, is highly homologous (51.9 % overall and 69.2 % in seven transmembrane regions) to human EDG-1, 47.9 % to rat AGR16 but only 28.0 % to human CB1 receptor. The Northern hybridization analysis showed that a 2.8 kb transcript of EDG-3 is abundantly expressed in the heart followed by placenta, kidney and liver. The EDG-3 gene was mapped on the human chromosome 9q22.1-q22.2 by fluorescence in situ hybridization analysis. Although the ligand and physiological role of this receptor is unknown, this gene may be a new member of the EDG family.

Amino Acid Sequence↗
PubMed1996

Genomic organization of the fungus Phycomyces.

The fungus Phycomyces blakesleeanus has a relatively small genome, 30 megabases (Mb), with a low guanine and cytosine (G + C) content, 35%; the coding sequences cloned to date all have a G + C content of about 50%. In order to investigate the organization of the genome of this fungus, we have cloned and sequenced 251 DNA fragments. One hundred and twenty-six clones were obtained by digestion with MspI (target sequence 5'-CCGG-3') and 125 random clones were obtained by sonication. The average length of sequence obtained was about 200 base pairs (bp) and the total length was about 50 kilobases (kb). The G + C content is not homogeneous throughout the genome: sequences obtained after digestion with MspI have an average of 5% more G + C content than the random fragments, and are enriched in coding sequences. Fourteen MspI fragments show similarities to known proteins and 21 encode ribosomal RNA (rRNA). By contrast, only three of the random fragments are similar to known proteins and only one to a rRNA. We conclude that the Phycomyces genome is composed of G + C-rich genes surrounded by G + C-poor areas. Two clones have similarities to the transposase of the transposon Tc1 from Caenorhabditis elegans. This result suggests the presence of a high copy number of a Tc1-like transposable element in the Phycomyces genome. Another clone was similar to the transposon Tx1 from Xenopus laevis. A novel repetitive nt sequence has been characterized; about 5% of the total genome is a repetition of any of two consensus sequences of 31 bp named PrA1 and PrA2.

Amino Acid Sequence↗