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Biomedical subjects

S Brenner

Publications and source records attributed to S Brenner.

At least 199 records · Page 11Linked to original sources
PubMed1995

Genomic structure and sequence of the Fugu rubripes glucose-6-phosphate dehydrogenase gene (G6PD).

To investigate the organization of the compact genome of the puffer fish Fugu rubripes at the level of an individual housekeeping gene, we have cloned and sequenced the glucose-6-phosphate dehydrogenase (G6PD) gene from this fish and compared it to the corresponding human gene. The intron/exon structure of the two genes is identical throughout the protein coding regions. The puffer fish gene is four times smaller than the human gene--the difference is accounted for by the fact that the puffer fish gene has smaller introns. Intron 2 is the largest intron in both species. We have constructed a molecular phylogeny for 10 G6PD protein sequences. The sequences fall in the expected arrangement based on established phylogenetic relationships, with the Plasmodium falciparum sequence the most widely diverged.

Amino Acid Sequence↗
PubMed1995

Loose ends.

Explore the source record for details and available documents.

Animals↗
PubMed1995

Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes.

Comparative vertebrate genome sequencing offers a powerful method for detecting conserved regulatory sequences. We propose that the compact genome of the teleost Fugu rubripes is well suited for this purpose. The evolutionary distance of teleosts from other vertebrates offers the maximum stringency for such evolutionary comparisons. To illustrate the comparative genome approach for F. rubripes, we use sequence comparisons between mouse and Fugu Hoxb-4 noncoding regions to identify conserved sequence blocks. We have used two approaches to test the function of these conserved blocks. In the first, homologous sequences were deleted from a mouse enhancer, resulting in a tissue-specific loss of activity when assayed in transgenic mice. In the second approach, Fugu DNA sequences showing homology to mouse sequences were tested for enhancer activity in transgenic mice. This strategy identified a neural element that mediates a subset of Hoxb-4 expression that is conserved between mammals and teleosts. The comparison of noncoding vertebrate sequences with those of Fugu, coupled to a transgenic bioassay, represents a general approach suitable for many genome projects.

Animals↗
PubMed1995

Analysis of the dopamine receptor family in the compact genome of the puffer fish Fugu rubripes.

The genome of the puffer fish, Fugu rubripes (Fugu), is approximately 400 Mb, 7.5 times smaller than that of human. We have isolated four dopamine receptor-like genes from Fugu genomic DNA. These genes show high sequence and structural homology to the known dopamine receptor genes, although, in contrast to previously described genes from this species, the intron size is comparable to that in human. The 5' noncoding exons of the D2/D3 dopamine receptor-like genes is described and compared to that in human. The high gene density of Fugu is shown by the close proximity of a cystatin-like gene 1503 bp from the dopamine receptor gene D222. We propose that the compact genome of Fugu can serve as a model for identifying gene family members directly from genomic DNA.

Amino Acid Sequence↗
PubMed1995

Comparative sequence analysis of the human and pufferfish Huntington's disease genes.

The Huntington's disease (HD) gene encodes a novel protein with as yet no known function. In order to identify the functionally important domains of this protein, we have cloned and sequenced the homologue of the HD gene in the pufferfish, Fugu rubripes. The Fugu HD gene spans only 23 kb of genomic DNA, compared to the 170 kb human gene, and yet all 67 exons are conserved. The first coding exon, the site of the disease-causing triplet repeat, is highly conserved. However, the glutamine repeat in Fugu consists of just four residues. We also show that gene order may be conserved over longer stretches of the two genomes. Our work describes a detailed example of sequence comparison between human and Fugu, and illustrates the power of the pufferfish genome as a model system in the analysis of human genes.

Amino Acid Sequence↗
PubMed1995

Effect of topical interferon-beta on recurrence rates in genital herpes: a double-blind, placebo-controlled, randomized study.

The aim of this randomized, double-blind placebo-controlled trial was to evaluate the effect of IFN-beta cream applied at the time of recurrent eruptions of genital herpes during 6 months on the overall rate of recurrence. Therapy was initiated at the clinic for the first treated recurrence, and thereafter by the patient for early treatment of eventual subsequent eruptions. Each recurrence was ascertained at the clinic in all 35 evaluable patients. The mean recurrence rate was significantly lower in the group using IFN-beta cream than in the placebo group (p = 0.03). Complete responders without recurrence for the duration of the trial were 36.4% of all patients and 46% among women versus 15.4 and 16.6% in the placebo groups, respectively. A total of 77.3% of all patients were defined as complete or partial responders, their average recurrences/year decreasing from 11 to 2.2 (p < 0.0001). The topical episodic IFN-beta treatment was well tolerated by patients and without side effects. It is concluded that IFN-beta cream application reduces the overall rate of recurrence of genital herpes.

Administration, Topical↗
PubMed1995

Organization of host-inducible transcripts on the symbiotic plasmid of Rhizobium sp. NGR234.

In a systematic approach to identify genes involved in the early steps of the legume-Rhizobium symbiosis, we studied transcription patterns of symbiotic plasmid-borne loci. A competitive hybridization procedure was used to identify DNA restriction fragments carrying genes whose expression is enhanced by plant root exudates or by purified flavonoids. Fragments containing induced genes were then located on the physical map of the 500 kb pNGR234a. New inducible loci as well as previously described genes were identified and their time course of induction determined. After initial induction, transcription of loci such as nodABC and the host-specificity genes nodSU decreased to undetectable levels 24 h after incubation with purified flavonoids. In contrast, expression of other loci is detectable only after several hours of induction. Surprisingly, many genes remained transcribed in the nodD1- mutant suggesting the presence of other flavonoid-dependent activators in NGR234. The hsnl region, which is involved in host specificity, was shown to carry several inducible but independently regulated transcripts. Sequencing analysis revealed several open reading frames whose products, based on sequence similarities, may be involved in L-fucose metabolism and its adjunction to the Nod factors.

Binding, Competitive↗
PubMed1995

Isotopic response.

BACKGROUND: The occurrence of a new skin disorder exactly at the site of another one, already healed and unrelated, was first described in 1955. In 1985, Wolf et al. recognized that we are dealing with a dermatologic phenomenon and established a precise definition for this phenomenon. Fifty-eight cases corresponding to the definition of this phenomenon have been reported until now. METHODS: The new phenomenon, for which the term "isotopic response" has been suggested, has been defined. Cases corresponding to the definition have been analyzed with special emphasis on the diseases involved, the time intervals, and the locations of the diseases. Eight new cases are described. RESULTS: A total of 58 cases of isotopic response have been described. The first disease in most of the patients was herpes zoster; in three cases it was herpes simplex, in two varicella, and in one, thrombophlebitis. The second disease, which appeared exactly at the site of the first, already healed disease, was in most reported cases a carcinoma (26 cases, in particular 15 cases of breast carcinoma, 5 basal cell carcinomas (BCC), 4 squamous cell carcinomas (SCC), 2 basosquamous carcinomas), or granuloma annulare (16 cases). Additional diseases were Kaposi's sarcoma (2 cases), pseudolymphoma (2 cases), sarcoid (2 cases), tinea (2 cases), tuberculoid and vasculitis granuloma (1 case), angiosarcoma, metastasis, Bowen's disease, lymphoma, leukemia cutis, and acne (1 case each). The diseases did not show any predilection for a particular location. The interval between the first and second disease was extremely variable (ranging from days to years) and showed no particular features. In the eight additional cases described in the present report, the first disease was herpes simplex (6 cases) or herpes zoster (2 cases). The second disease was viral warts (3 cases) or squamous cell carcinoma (2 cases). Additional diseases were furunculosis, contact dermatitis, and molluscum contagiosum (1 case each). CONCLUSIONS: The new term, "isotopic response," describes the occurrence of a new skin disorder at the site of another, unrelated, and already healed skin disease. It is suggested that the term "isotopic response" be included in the lexicon (glossary) of dermatology. Introducing the new term and classifying all the cases under a single key word, will make it possible to locate and collect them easily and to search for the mechanism underlying this phenomenon.

Aged↗
PubMed1995

Another "paraben paradox".

BACKGROUND: To test the reliability and reproducibility of the patch test with a paraben mix, we added a second paraben mix allergen to our standard tray and compared the results achieved with these two allergens. METHODS: Two hundred and fifteen consecutive patients, undergoing patch testing with a standard series, were simultaneously tested with an additional paraben mix (i.e., each patient was tested with two paraben mix allergens) supplied by two different companies. RESULTS: Twelve patients (5.6%) showed a positive reaction to one or two paraben tests. Five patients showed a positive reaction to one paraben test (paraben-a), and five others to the second paraben test (paraben-b). Only two patients out of 12 with positive reactions to parabens showed a reaction with both of the two parabens. The parabens appear to be overrepresented in our study compared to other series. There was no correlation between the results of the tests with the two different parabens used. CONCLUSIONS: Patch testing with a paraben mix cannot be considered an appropriate and reliable method for detecting paraben allergies. It is recommended to test routinely with a paraben screening series instead of the paraben mix.

Allergens↗
PubMed1995

Pemphigus and dietary factors. In vitro acantholysis by allyl compounds of the genus Allium.

BACKGROUND: Today it is generally accepted that every drug that possesses an active thiol group in its molecule is capable of inducing pemphigus in vivo and provoking acantholysis in vitro. We therefore suggested that plants, in particular those belonging to the Allium group, that contain several active compounds with stable disulfide and thiol groups in their molecule may cause the same. OBJECTIVE: To verify this hypothesis by investigating the in vitro acantholytic effect of three compounds of garlic. METHODS: Skin samples from donors were cultured in the presence of three compounds of garlic (i.e. allylmercaptan, allylmethylsulfide and allylsulfide) for 3 days. The skin samples were then processed for microscopic control for acantholysis. RESULTS: Results indicate that, indeed, the three garlic compounds tested are capable of inducing acantholysis in vitro. Focal and diffuse acantholysis was observed in the specimens from 4 out of 7 donors cultured in the presence of 6 and 9 mM of each of the allyl compounds for 3 days. Interestingly, tissues from a DR4+ donor proved to be more acantholysis prone than others, showing large blistering due to diffuse acantholysis, thus indicating that individual susceptibility plays a crucial role also in vitro. CONCLUSION: Garlic compounds with stable disulfide and thiol groups in their molecule are capable of inducing acantholysis in vitro. These findings lend further support to the theory that 'harmless' nutritional factors are capable of inducing acantholysis in vitro and possibly also in vivo. In view of these findings, it is suggested that nutritional factors should be added to the ever-growing list of exogenous factors capable of inducing pemphigus.

Acantholysis↗
PubMed1995

Identical HLA class II alleles predispose to drug-triggered and idiopathic pemphigus vulgaris.

In pemphigus vulgaris, a dermatological autoimmune disease, specific human leukocyte antigen (HLA) class II alleles, DR4 (DRB1*0402) and DRw14 (DRB1*1401, in linkage disequilibrium with DQB1*0503), are thought to be susceptibility genes involved in the onset of the disease. We studied the HLA class II alleles (DQA1, DQB1, DRB1 and DPB1) of 6 patients with pemphigus, in whom the disease was "triggered" by drugs containing sulphydryl or another sulphur-containing group. All patients carried the DRB1*0402 susceptibility allele, and one patient also carried the second susceptibility allele, namely DQB1*0503 (in linkage with DRB1*1401). Bacterial, viral or environmental agents are suspected to trigger the onset of autoimmune diseases. Our study demonstrated the presence in patients with drug-triggered pemphigus vulgaris of the same HLA alleles thought to predispose to idiopathic pemphigus vulgaris. This finding strengthens the notion that these HLA alleles may be true disease susceptibility genes.

Adult↗
PubMed1995

Scabies: the diagnosis of atypical cases.

In the current scabies pandemic, classic scabies is seen less frequently and special forms are becoming more common. The diagnosis of scabies has become, therefore, a challenge for clinicians. The well-known scabietic burrow is seen only very rarely today and, therefore, pathognomonic as it is, the diagnosis of scabies should not rely on this clinical sign. In our experience, examination of skin scrapings mounted on a slide with saline is the most practical bedside method and ideal for screening patients with suspected scabies. It is easy to perform, requires neither sophisticated tools nor special skill, and can be done in less than five minutes by every practitioner.

Animals↗
PubMed1995

Structure and organization of the isotocin and vasotocin genes from teleosts.

Oxytocin and vasopressin are structurally related mammalian neurohypophysial hormones with distinct physiological activities. Homologues of these two hormones are found in all vertebrate groups except the primitive cyclostomes in which only a vasopressin-like hormone has been reported so far. Genes encoding the mammalian oxytocin and vasopressin hormone precursors exhibit a similar genomic organisation, and are closely linked (3.5 kb to 12 kb apart) in a tail-to-tail manner suggesting a common evolutionary origin. However, no linkage among genes of the vasopressin/oxytocin family has been demonstrated in any of the lower vertebrates. The Japanese pufferfish, Fugu rubripes, has been shown to have a very compact genome of about 400 Mb with very few repetitive sequences. We used this model vertebrate genome to analyse the genomic organisation of vasotocin and isotocin genes, the teleost homologues of vasopressin and oxytocin. We have cloned and mapped the vasotocin/isotocin locus in Fugu and obtained complete nucleotide sequences of the vasotocin and isotocin genes. The coding sequences of the Fugu vasotocin and isotocin genes are interrupted by two introns at identical positions, similar to their homologues in higher vertebrates. The deduced amino acid sequences as well as the coding sequences of the two genes show high homology in the neurophysin region. Furthermore, the two genes are linked in a tandem manner with an intergenic region of about 20 kb. Random sequencing has shown that there are at least two known vertebrate genes in the intergenic region. Genomic organisation of the Fugu vasotocin/isotocin locus suggests that the teleost vasotocin and isotocin genes have evolved from a common ancestor through tandem duplication and that this locus seems to have undergone a localised reorganisation during vertebrate evolution.

Amino Acid Sequence↗
PubMed1994

Recursive deconvolution of combinatorial chemical libraries.

A recursive strategy that solves for the active members of a chemical library is presented. A pentapeptide library with an alphabet of Gly, Leu, Phe, and Tyr (1024 members) was constructed on a solid support by the method of split synthesis. One member of this library (NH2-Tyr-Gly-Gly-Phe-Leu) is a native binder to a beta-endorphin antibody. A variation of the split synthesis approach is used to build the combinatorial library. In four vials, a member of the library's alphabet is coupled to a solid support. After each coupling, a portion of the resin from each of the four reaction vials was set aside and catalogued. The solid support from each vial is then combined, mixed, and redivided. The steps of (i) coupling, (ii) saving and cataloging, and (iii) randomizing were repeated until a pentapeptide library was obtained. The four pentapeptide libraries where the N-terminal amino acid is defined were screened against the beta-endorphin antibody and quantitated via an ELISA. The amino acid of the four pools that demonstrated the most binding was then coupled to the four tetrapeptide partial libraries that had been set aside and catalogued during the split synthesis. This recursive deconvolution was repeated until the best binders were deduced. Besides the anticipated native binder, two other members of the library displayed significant binding. This recursive method of deconvolution does not use a molecular tag, requires only one split synthesis, and can be applied to the deconvolution of nonlinear small-molecule combinatorial libraries and linear oligomeric combinatorial libraries, since it is based only on the procedure of the synthesis.

Amino Acid Sequence↗