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Biomedical subjects

S Brenner

Publications and source records attributed to S Brenner.

At least 181 records · Page 10Linked to original sources
PubMed1996

Conserved linkage between the puffer fish (Fugu rubripes) and human genes for platelet-derived growth factor receptor and macrophage colony-stimulating factor receptor.

We have cloned and sequenced the teleost homologs of the human genes encoding platelet-derived growth factor receptor-beta (PDGFR beta) and macrophage colony-stimulating factor 1 receptor (CSFIR) from the puffer fish Fugu rubripes. The Fugu PDGFR beta and CSFIR genes each consist of 21 coding exons similar to the human CSFI gene, but are considerably smaller than their human counterparts because of the smaller introns. Furthermore, the two Fugu genes are linked tandemly in a head-to-tail array similar to their human homologs with 2.2 kb of intergenic sequence. Amino acid sequences of the Fugu and human PDGFR beta and CSFIR genes show an overall homology of 45% and 39%, respectively, with the kinase domains showing a much higher degree of conservation. Dot-matrix analysis revealed several short stretches of conserved sequences in the 3' untranslated regions of the PDGFR beta genes and the adjacent promoter regions of the CSFIR genes. These conserved sequences may have a role in the regulation of expression of either or both of these closely linked genes.

Amino Acid Sequence↗
PubMed1996

G protein alpha subunit multigene family in the Japanese puffer fish Fugu rubripes: PCR from a compact vertebrate genome.

We compare the complexity and organization of the G protein alpha subunit multigene family in the vertebrate genomes of mammals and the Japanese puffer fish Fugu rubripes. Fourteen Fugu G alpha genes were identified of the 16 genes characterized previously in mammals, including Fugu genes from the four classes of alpha subunits Gs, Gi, Gq, and G12. Fugu and mammalian G alpha coding sequences are highly homologous, and the intron/exon structure of the fish and mammalian orthologs is identical throughout the coding regions. A novel G alpha gene, G alpha p1, was also identified in Fugu rubripes and two other species of puffer fish. The complete sequence of Gnaz and the tandemly duplicated genes Gnai2 and Gnat1 were obtained from a Fugu genomic cosmid library. Introns in the puffer fish G alpha genes lacked repeat DNA sequences, other than simple sequence length repeats, and most introns were significantly shorter in Fugu than in mammalian orthologs. The compact genome of puffer fish provides a unique vertebrate model for characterizing multigene families and identifying novel genes directly from genomic DNA by PCR amplification with degenerate primers. The fact that Fugu encodes most, if not all, of the G protein alpha subunits identified in mammals strongly supports Fugu as a model organism for vertebrate genome research.

Amino Acid Sequence↗
PubMed1996

Fugu intron oversize reveals the presence of U15 snoRNA coding sequences in some introns of the ribosomal protein S3 gene.

We present here the analysis of the genomic organization of the Fugu gene coding for ribosomal protein S3 and its intron encoded U15 RNA, and compare it with the homologous human and Xenopus genes. Only two of the six Fugu S3 gene introns do not contain the U15 sequence and are in fact shorter than 100 nucleotides, as most Fugu introns. The other four introns are somewhat longer and contain sequences homologous to U15 RNA; two of these represent functional copies, as shown by microinjections of Fugu transcripts into Xenopus oocytes, whereas the other two appear to be nonfunctional pseudocopies. Thus Fugu turns out to be ideal for the study of intron encoded snoRNAs, partly because of the reduced cloning and sequencing workload, and partly because the intron length per se can be an indication of the presence of a snoRNA coding sequence.

Animals↗
PubMed1996

Supplemental tests in the evaluation of occupational hand dermatitis in soldiers.

BACKGROUND: Hand dermatitis in soldiers is a considerable problem. The purpose of the study was to evaluate appropriate screening tests to improve the diagnosis of hand dermatitis in soldiers. MATERIALS AND METHODS: A group of 111 soldiers with occupational dermatitis from contact with fuels and oils underwent "tailored patch tests" with allergens relevant to their field of work and their environment. The control group consisted of 24 soldiers with various jobs similar to those of civilian life, who had not been exposed to oils and fuels. Seventy-three civilian patients, attending the clinic for patch testing, were also included. Twenty soldiers, who had a history of intensive contact with oil and fuels, but no contact dermatitis, and who were admitted because of various skin diseases (fungal infections, acne, etc.) also underwent the supplemental testing and served as an additional control group. RESULTS: Of the soldiers, 31 (29%) showed one or more positive skin tests of the oil series and 30 patients of this group one or more positive reactions to the standard patch tests trays. No patient of the control groups had a positive test to the oil series. CONCLUSIONS: Our results show the value of the supplementary tests as a first-step screening test for detection of oil allergy in soldiers and automobile-mechanics or in workers handling other gasoline- or diesel-powered engineering equipment. The test method appears to be practical, easy to perform, reliable and giving clear and accurate results, with a negligible rate of false positive reactions.

Allergens↗
PubMed1996

Inhibition of proliferation of psoriatic and healthy fibroblasts in cell culture by selected Dead-sea salts.

The effect of five selected minerals abundant in the Dead-sea brine was studied on proliferation of fibroblasts grown from psoriatic and healthy skin biopsy specimens in cell culture. The reason for carrying out this study was looking for the mechanism of the antiproliferative effect of selective Dead-sea minerals in improving the psoriatic condition. Psoriatic skin shave biopsy specimens (both from involved and uninvolved areas of the body) as well as healthy skin (obtained from amputated limbs) were incubated in tissue culture, and their outgrowing fibroblasts were used for this study. The number of cells and their cyclic AMP content were used as parameters for cell division and for proving the selective involvement of magnesium salts in the antiproliferative effect. It is shown that the inhibitory effects of magnesium bromide and magnesium chloride on cell growth were significantly stronger than those of their corresponding potassium salts or of sodium chloride. These results were obtained with both psoriatic and healthy skin fibroblasts, indicating that the inhibitory effect of the selected Dead-sea minerals is present in healthy and psoriatic skin cells.

Baths↗
PubMed1996

Topical treatment with 1% sodium cromoglycate in pyoderma gangrenosum.

BACKGROUND: Pyoderma gangrenosum is an uncommon skin disease usually treated with systemic drugs, most frequently corticosteroids. Isolated topical treatment is usually considered unsatisfactory. OBJECTIVE: To evaluate the effect of topical 1% sodium cromoglycate solution on pyoderma gangrenosum in 5 patients 25-30 years of age. METHODS: 5 patients, including 2 under systemic steroid treatment, hospitalized in our department from 1992 to 1993 because of pyoderma gangrenosum, were treated with topical 1% sodium cromoglycate solution. Systemic corticosteroids were further added in 2 patients whose initial improvement was inadequate. RESULTS: Initial improvement was noted in all 5 patients after 3-7 days of sodium cromoglycate treatment. Complete healing of the ulcers occurred within 5-8 weeks. CONCLUSIONS: Topical treatment with sodium cromoglycate can be effective as adjunctive or sole treatment in pyoderma gangrenosum.

Administration, Topical↗
PubMed1996

A case of diet-related pemphigus.

An experimental investigation has lately shown that certain allyl compounds of garlic are able to provoke acantholysis in normal human skin cultured in vitro. The acantholytic effect has been more prominent in the samples from DR4+ donor. We here report a case of superficial pemphigus which appeared spontaneously in a DR4,14+, 49-year-old man and which ran a course that proved to be affected by dietary factors, in particular by the consumption of garlic. In the absence of a conventional treatment and on a garlic-free diet only, the disease ceased for several months. Soon after an unintentional dietary test with a strongly and presumable garlic-spiced fish meal, the pemphigus recurred. Nutritional factors should be added to the ever-growing list of exogenous factors capable of inducing or perpetuating pemphigus in genetically predisposed individuals.

Diet↗
PubMed1996

Treatment of Kaposi's sarcoma.

The classic form of Kaposi's sarcoma (KS) is a rare multifocal neoplasm, as described by Kaposi in 1872. One hundred nine years after Kaposi's first description of the disease, the interest in all aspects of this disease escalated because of the emergence of human immunodeficiency virus (HIV), which is frequently accompanied by KS. This prompted zealous research, as reflected by numerous reports. Despite recent important discoveries, we are still far from understanding the pathogenesis of the disease and the mechanism of action of its various treatment modalities. As of today, treatment consists of most of the old modalities, some old ones in an updated improved version, and some new and experimental therapies. Our purpose is to focus on recent or novel data and to mention available treatments and their advantages, disadvantages, and side effects. We will also speculate on future directions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Scrofuloderma (tuberculosis colliquativa cutis).

A 16-year-old girl presented with long-standing purulent sinuses to the skin overlying the lacrimal ducts, which had evolved into ulcers and resulted in hypertrophic scarring. The ulcers were serpiginous, with an uneven soft floor, and undermined edges. Histological examination revealed non-caseating tuberculoid granulomas in the dermis. Cultures for Mycobacterium tuberculosis were positive. Chest X-ray did not show pulmonary involvement. Antituberculous therapy with isoniazid 300 mg/day and rifampicin 600 mg/day achieved a great improvement within 5 weeks of being started. A further improvement was seen at 4 months and complete resolution had occurred by 9 months. To the best of our knowledge, there are no other documented cases of scrofuloderma over the lacrimal system. The delay in the diagnosis emphasizes the importance of maintaining a high level of awareness.

Adolescent↗
PubMed1995

Liquid-phase combinatorial synthesis.

A concept termed liquid-phase combinatorial synthesis (LPCS) is described. The central feature of this methodology is that it combines the advantages that classic organic synthesis in solution offers with those that solid-phase synthesis can provide, through the application of a linear homogeneous polymer. To validate this concept two libraries were prepared, one of peptide and the second of nonpeptide origin. The peptide-based library was synthesized by a recursive deconvolution strategy [Erb, E., Janda, K. D. & Brenner, S. (1994) Proc. Natl. Acad. Sci. USA 91, 11422-11426] and several ligands were found within this library to bind a monoclonal antibody elicited against beta-endorphin. The non-peptide molecules synthesized were arylsulfonamides, a class of compounds of known clinical bactericidal efficacy. The results indicate that the reaction scope of LPCS should be general, and its value to multiple, high-throughput screening assays could be of particular merit, since multimilligram quantities of each library member can readily be attained.

Amino Acid Sequence↗
PubMed1995

Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx.

Comparison of Hoxb-1 regulatory regions from different vertebrates identified three related sequence motifs critical for rhombomere 4 (r4) expression in the hindbrain. Functional analysis in transgenic mice and Drosophila embryos demonstrated that the conserved elements are involved in a positive autoregulatory loop dependent on labial (lab) family members. Binding of Hoxb-1 to these elements in vitro requires cofactors, and the motifs closely resemble the consensus binding site for pbx1, a homolog of the Drosophila extradenticle (exd) homoedomain protein. In vitro exd/pbx serves as a Hoxb-1 cofactor in cooperative binding and in Drosophila expression mediated by the r4 enhancer is dependent on both lab and exd. This provides in vivo and in vitro evidence that r4 expression involves direct autoregulation dependent on cooperative interactions of Hoxb-1 with exd/pbx proteins as cofactors.

Animals↗
PubMed1995

Genomic structure and nucleotide sequence of the p55 gene of the puffer fish Fugu rubripes.

The p55 gene, which codes for a 55-kDa erythrocyte membrane protein, has been cloned and sequenced from the genome of the Japanese puffer fish Fugu rubripes (Fugu). This organism has the smallest recorded vertebrate genome and therefore provides an efficient way to sequence genes at the genomic level. The gene encoding p55 covers 5.5 kb from the beginning to the end of the coding sequence, four to six times smaller than the estimated size of the human gene, and is encoded by 12 exons. The structure of this gene has not been previously elucidated, but from this and other data we would predict a similar or identical structure in mammals. The predicted amino acid sequence of this gene in Fugu, coding for a polypeptide of 467 amino acids, is very similar to that of the human gene with the exception of the first two exons, which differ considerably. The predicted Fugu protein has a molecular weight (52.6 kDa compared with 52.3 kDa) and an isoelectric point very similar to those of human p55. In human, the p55 gene lies in the gene-dense Xq28 region, just 30 kb 3' to the Factor VIII gene, and is estimated to cover 20-30 kb. Its 5' end is associated with a CpG island, although there is no evidence that this is the case in Fugu. The small size of genes in Fugu and the high coding homology that they share with their mammalian equivalents, both in structure and sequence, make this compact vertebrate genome an ideal model for genomic studies.

Amino Acid Sequence↗