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Biomedical subjects

S Brenner

Publications and source records attributed to S Brenner.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Encoded combinatorial chemistry.

The diversity of chemical synthesis and the power of genetics are linked to provide a powerful, versatile method for drug screening. A process of alternating parallel combinatorial synthesis is used to encode individual members of a large library of chemicals with unique nucleotide sequences. After the chemical entity is bound to a target, the genetic tag can be amplified by replication and utilized for enrichment of the bound molecules by serial hybridization to a subset of the library. The nature of the chemical structure bound to the receptor is decoded by sequencing the nucleotide tag.

Amino Acid Sequence↗
PubMed1992

Clustering cDNA sequences.

A set of programs has been written to quantify the similarities between large numbers of cDNA sequences. This information is used to cluster similar sequences together. The main program can cluster thousands of cDNA sequences per day using a novel, computationally inexpensive algorithm. The clustering information is kept in a small index file so that disk storage requirements are negligible. Using this index file, subsidiary programs create various views and statistical summaries of the entire cDNA sequence collection.

Algorithms↗
PubMed1992

Systemic ketoconazole treatment for Fusarium leg ulcers.

Fusarium oxysporum was isolated from a large foot ulcer in an otherwise healthy 69-year-old man. Although tissue invasion could not be proven histologically, systemic antifungal treatment was administered with satisfactory response. Fusarium species are common soil-inhabiting organisms and plant pathogens. In humans, Fusarium is considered an opportunistic agent in skin ulcers, interdigital spaces, and burned skin, but can also cause mycotic keratitis, onychomycosis, and rarely deep-seated or disseminated infections, especially in an immunocompromised host. The distinction between skin infection and saprophytic growth, as well as optimal treatment regimens for the two types of infection, have not been clearly defined. We describe a case of leg ulcers caused by Fusarium oxysporum in a 69-year-old man treated successfully with oral ketoconazole. "Silent" immunologic disturbances were found in this apparently healthy patient. The case illustrates a relatively benign infection caused by Fusarium that responded to systemic antifungal drug treatment.

Aged↗
PubMed1992

Expression of the mosquitocidal toxins of Bacillus sphaericus and Bacillus thuringiensis subsp. israelensis by recombinant Caulobacter crescentus, a vehicle for biological control of aquatic insect larvae.

In the quest for effective control of mosquitoes, attention has turned increasingly to strains of the bacteria Bacillus sphaericus and Bacillus thuringiensis subsp. israelensis, which produce potent toxins with specific mosquitocidal activities. However, sedimentation of the bacterial spores limits the duration of effective control after field application of these bacilli. We describe here the cloning of genes encoding the 51.4- and 41.9-kDa toxins from B. sphaericus 2297, the 100-kDa toxin from B. sphaericus SSII-1, and the 130-kDa toxin from B. thuringiensis subsp. israelensis into the broad-host-range plasmid pRK248 and the transfer of these genes for expression in Caulobacter crescentus CB15. The recombinant C. crescentus cells were shown to be toxic to mosquito larvae. Caulobacter species are ubiquitous microorganisms residing in the upper regions of aquatic environments and therefore provide the potential for prolonged control by maintaining mosquitocidal toxins in larval feeding zones.

Animals↗
PubMed1992

Extreme airborne asbestos concentrations in a public building.

Fibre concentrations of asbestos were measured in the air of a communal dining room in which the damaged ceiling had a sprayed on coating of insulation containing asbestos. The average concentration of crocidolite asbestos fibres was 4 f/cm3, 20 times the highest air concentration that appears to have been reported previously for a public building. It is concluded that although air concentrations of asbestos fibres in public buildings containing asbestos insulation materials are usually low, high concentrations can occur. This may have implications for the risk of exposed persons developing diseases associated with asbestos.

Air Pollution, Indoor↗
PubMed1992

Cutaneous blood flow measurements for the detection of malignancy in pigmented skin lesions.

This work assesses cutaneous blood flow measurements as an adjunct in the differentiation between malignant and benign pigmented skin lesions. Blood flow in pigmented lesions and in their vicinity was measured by laser Doppler flowmetry (LDF), which measures the superficial skin blood flow. The lesions were then excised and histologically examined. While LDF readings for most of the benign lesions did not differ from those of control measurements, basal cell carcinomas showed a significant elevation and so did the melanomas (p less than 0.0001). Moreover, comparing the two groups of malignant lesions, namely the melanomas and basal cell carcinomas, the melanomas showed a significantly higher elevation (p less than 0.02). These results suggest that LDF may serve as an additional tool in the diagnosis of pigmented skin lesions: the probability of malignancy is low when LDF readings show no difference from adjacent normal skin; on the contrary, elevated readings suggest an increased likelihood of malignancy.

Blood Flow Velocity↗
PubMed1992

Langerhans' cell distribution in drug eruption.

The number in and distribution of Langerhans' cells were studied in 11 patients with a maculopapular drug eruption. The Langerhans' cells (LC) were identified with a monoclonal antibody to OKT6 antigen, by employing an immunofluorescence technique. Skin biopsies were taken from lesional and non-lesional skin during the acute stage of the disease. LC in the lesional biopsies increased in number by 66% (p less than 0.001) and displayed more intense staining and more prominent dendrites than did LC from non-lesional skin. Control biopsies, taken from identical sites at least 4 weeks after the eruption disappeared, exhibited a cell distribution similar to the non-lesional acute stage (p = N.S.). Delivery of drugs via the circulation and their distribution into the skin may cause a type IV immune reaction due to LC activation by a drug-carrier complex.

Acute Disease↗
PubMed1992

Intertriginous drug eruption.

Presented are two patients who developed an unusual, and as yet unreported eruption due to amoxycillin. They exhibited an eruption confined to the intertriginous areas, which mimicked intertrigo. Although drug eruption can mimic a variety of idiopathic skin diseases, intertrigo is easily distinguished from drug eruption and has not been mentioned in the differential diagnosis of this reaction. It is suggested that drug reactions should be considered in the differential diagnosis of intertrigo, in particular of atypical and therapy-resistant cases. Early detection of these cases has practical importance since the elimination of the causative drug is essential for therapy success. Case 2 showed a response of the toxic epidermal neurolysis (TEN) type, which could have been very severe and dangerous had the diagnosis not been made in an early stage before the development of generalized TEN.

Adult↗