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Biomedical subjects

S Brenner

Publications and source records attributed to S Brenner.

At least 235 records · Page 13Linked to original sources

Characterization of the pufferfish (Fugu) genome as a compact model vertebrate genome.

Cloning and sequencing techniques now allow us to characterize genes directly instead of having to deduce their properties from their effects. This new genetics reaches its apotheosis in the plan to obtain the complete DNA sequence of the human genome, but this is far beyond the capacity of present sequencing methods. Small 'model' genomes, 'such as those of Escherichia coli (4.7 megabases (Mb) and yeast (14 Mb), or even those of Caenorhabditis elegans (100 Mb) and Drosophila (165 Mb), are better scaled to existing technology. The yeast genome will contain genes with functions common to all eukaryotic cells, and those of simple multicellular organisms may throw light on the genetic specification of more complex functions. However, vertebrates differ in their morphology and development, so the ideal model would be a vertebrate genome of minimum size and complexity but with maximum homology to the human genome. Here we report the characterization of the small genome (400 Mb) of the tetraodontoid fish, Fugu rubripes. A random sequencing approach supported by gene probing shows that the haploid genome contains 400 Mb of DNA, of which more that 90% is unique. This genome is 7.5 times smaller than the human genome and because it has a similar gene repertoire it is the best model genome for the discovery of human genes.

Animals↗

Vectors lambda 200g and lambda 200c: two useful derivatives of lambda 2001.

We describe the construction and uses of two new phage lambda replacement vectors. Both are modifications of lambda 2001 which allows selection of cloned inserts by the Spi- phenotype, following the replacement of a gam+ filler fragment. Vector lambda 200g has a second gam gene with an amber mutation in its right arm which enables the selection of clones with inserts in the normal way in Su0 host bacteria and the maintenance of their genetic stability by subsequent growth in Su+ strains. Vector lambda 200c is designed for complementation studies. It contains a cat gene and the attP site of lambda. Recombinants can be inserted into the bacterial chromosome or into an episome with the aid of appropriate helpers.

Attachment Sites, Microbiological↗

Topical tretinoin treatment in basal cell carcinoma.

BACKGROUND: The efficiency of topical tretinoin was examined in a patient with basal cell carcinomas (BCC) for which conventional means of removal was inappropriate. METHODS: Topical tretinoin was used to treat multiple arsenic-induced superficial BCCs in a 64-year-old woman. Topical tretinoin (0.05% twice daily) was administered to four lesions for 3 weeks followed by a 3-week interruption. RESULTS: After three cycles of treatment clinical healing of all the lesions was observed. Histopathological examination of the lesional biopsies showed no evidence of a tumor. However, 9 months later all four lesions relapsed and surgical excision disclosed BCC. CONCLUSION: The data indicate that topical tretinoin treatment of multiple superficial BCCs induces clinical and pathological regression of the lesions with a high rate of relapse. This report suggests that topical tretinoin is not an effective therapy for the cure of arsenic-induced superficial BCCs.

Administration, Cutaneous↗

Risk of melanoma after treatment of pigmented lesions with Solcoderm.

A 40-year-old patient developed a 5-mm-deep melanoma from a lesion on her chest which had been treated with Solcoderm 10 years previously. We recently described 3 other cases of melanoma that evolved in a lesion treated by Solcoderm. Much debate surrounds the recommendation as to the appropriate method for treatment of pigmented lesions when the removal is indicated for cosmetic reasons only. Most of the authors agree that any pigmented lesion which merits excision merits submission for histological examination. The aim of the present report was to express a warning regarding what we think is an inappropriate and hazardous method of treating pigmented lesions, namely their chemical destruction with Solcoderm. In view of the reported cases of melanoma evolving in lesions treated previously with Solcoderm, we believe that this treatment is absolutely contraindicated for pigmented lesions.

Acetates↗

SAPHO syndrome.

Four women with pustulosis palmoplantaris (PPP) and associated sternocostoclavicular hyperostosis are described. The connection between the two diseases is not coincidental: it is encountered in 9.4% of PPP patients, and was reported in the French literature as part of the SAPHO (synovitis acne pustulosis hyperostosis osteomyelitis) syndrome. This syndrome is linked to the spondyloarthropathies, having an increased prevalence of HLA B27 and occurrence of sacroiliitis. None of our patients had HLA B27, but HLA A26 was found in the 3 patients examined. No conclusion can be drawn from this finding, however, since this antigen is found in 21.7% of Ashkenazi Jews. Recognition of this syndrome by dermatologists will improve diagnosis and treatment.

Acne Vulgaris↗

Cutaneous paraneoplastic syndromes.

A review of a variety of cutaneous paraneoplastic conditions is presented. Although the conditions discussed appear in only 7-15% of cancer patients, they are considered indicators of possible underlying malignancy.

Humans↗

Low dose recombinant interferon alfa treatment for classic Kaposi's sarcoma.

BACKGROUND: High doses of interferon alfa are used to treat Kaposi's sarcoma in patients with immunodeficiency, whereas low doses are generally ineffective. Following low-dose recombinant interferon alfa treatment for lymphoma, two patients showed a regression of their hematologic malignancy-associated Kaposi's sarcoma. This observation prompted us also to try low-dose interferon alfa treatment in uncomplicated classic Kaposi's sarcoma, and two additional patients were thus treated on an outpatient basis. OBSERVATIONS: Initial response was noted after 3 to 13 weeks of treatment. Remission was achieved after 4 to 6 months of low-dose interferon alfa treatment and its duration was 8 to 14 months. Recurrences were treated again and additional remissions were obtained after only 5 to 8 weeks of treatment. CONCLUSION: Low-dose interferon alfa treatment may represent an effective therapeutic modality for the treatment of patients with both lymphoma-associated and uncomplicated classic Kaposi's sarcoma.

Aged↗

Methyldopa hypersensitivity syndrome.

A 74-year-old man developed an extensive erythematous skin eruption, fever, lymphadenopathy and eosinophilia probably due to methyldopa. The symptoms reappeared shortly after unintentional reexposure to the drug. The positive results of two in vitro tests for the detection of drug allergy not only give further support to the causal relationship between the drug and the symptoms, but also indicate the involvement of an immunologic, allergic mechanism. Although every individual symptom represented in our case has been reported in previous cases, the association of the symptoms together in one patient has never before been reported. An awareness that adverse reactions to methyldopa can mimic a variety of acute infectious diseases and lymphoproliferative disorders is the key to diagnosis and might prevent unnecessary hospitalizations, procedures, and use of potentially toxic antibiotics and chemotherapy.

Aged↗

Transfer of bacteria associated with cryotherapy.

The aim of this study was to determine whether living bacteria can be transmitted by cryosurgery with carbon dioxide. Cultures were taken from the outer layer of the ice before starting treatment, and again at the end of the working day during ten consecutive working days. Each of ten dry ice blocks was sterile prior to use. Staphylococcus epidermidis was isolated from six of the latter following use. This finding indicates that the dry ice was contaminated during the procedure and that bacteria were transmitted from the patient's skin to the dry ice and to culture media. The medical implications of this finding require serious consideration regarding the risk of infection to both patient and clinical personnel from this procedure.

Cryosurgery↗

The Caenorhabditis elegans unc-13 gene product is a phospholipid-dependent high-affinity phorbol ester receptor.

The Caenorhabditis elegans unc-13 mutant is a member of a class of mutants that have un-coordinated movement. Mutations of the unc-13 gene cause diverse defects in C. elegans, including abnormal neuronal connections and modified synaptic transmission in the nervous system. unc-13 cDNA encodes a protein (UNC-13) of 1734 amino acid residues with a predicted molecular mass of 198 kDa and sequence identity to the C1/C2 regions but not to the catalytic domain of the ubiquitously expressed protein kinase C family [Maruyama & Brenner (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 5729-5733]. To characterize the phorbol ester binding site of the UNC-13 protein, cDNA encoding the C1/C2-like regions (amino acid residues 546-940) was expressed in Escherichia coli and the 43 kDa recombinant protein was purified. Phorbol ester binding to the 43 kDa protein was zinc- and phospholipid-dependent, stereospecific and of high affinity (Kd 67 nM). UNC-13 specific antisera detected a protein of approx. 190 kDa in wild-type (N2) but not in mutant (e1019) C. elegans cell extracts. We conclude that UNC-13 represents a novel class of phorbol ester receptor.

Amino Acid Sequence↗

A selective lambda phage cloning vector with automatic excision of the insert in a plasmid.

A bacteriophage lambda cloning vehicle has been constructed for the generation of cDNA libraries. The vector has the following properties. (1) It has a unique BamHI site engineered into the lambda gam gene. Segments of DNA can be cloned into this site and clones with an insert can be selected by their ability to grow on an Escherichia coli host lysogenic for phage P2 (Spi- phenotype). (2) When the recombinant phage infects a Cre-producing E. coli strain, a site-specific recombination event results in the excision of a plasmid replicon with the cloned insert. (3) Single-stranded DNAs can be recovered by growing helper M13 phages on bacteria harboring such plasmids. The vector, lambda MGU2, has been used to construct a nematode (Caenorhabditis elegans) cDNA library.

Amino Acid Sequence↗