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S Brenner

Publications and source records attributed to S Brenner.

At least 109 records · Page 6Linked to original sources
PubMed1998

Changes in the periplasmic linker and in the expression level affect the activity of ToxR and lambda-ToxR fusion proteins in Escherichia coli.

In order to assess the potentiality of Vibrio cholerae ToxR protein and of bacteriophage lambda repressor as indicators of the dimerization of periplasmic proteins in Escherichia coli, we have constructed a series of plasmids encoding transmembrane fusion proteins. The amino-terminal part, containing the DNA binding domain of either ToxR or lambda repressor, is located in the cytoplasm and acts as reporter for dimerization. As models of periplasmic proteins we have used alkaline phosphatase (a dimer) and beta-lactamase (a monomer). Both the expression level and the distance between the transmembrane segment and the periplasmic protein substantially affect the activity of the reporter domains.

Alkaline Phosphatase↗
PubMed1998

Net prophets

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Journal Article↗
PubMed1998

The neural cell adhesion molecule L1: genomic organisation and differential splicing is conserved between man and the pufferfish Fugu.

The human gene for the neural cell adhesion molecule L1 is located on Xq28 between the ALD and MeCP2 loci. Mutations in the L1 gene are associated with four related neurological disorders, X-linked hydrocephalus, spastic paraplegia (SPG1), MASA syndrome, and X-linked corpus callosum agenesis. The clinical relevance of L1 has led us to sequence the L1 gene in human and to investigate its conservation in the vertebrate model genome of the pufferfish, Fugu rubripes (Fugu), a species with a compact genome of around 40Mb. For this purpose we have sequenced a human and a Fugu cosmid clone containing the corresponding L1 genes. For comparison, we have also amplified and sequenced the complete Fugu L1 cDNA. We find that the genomic structure of L1 is conserved. The human and Fugu L1 gene both have 28 exons of nearly identical size. Differential splicing of exons 2 and 27 is conserved over 430 million years, the evolutionary time span between the teleost Fugu and the human L1 gene. In contrast to previously published Fugu genes, many introns are larger in the Fugu L1 gene, making it slightly larger in size despite the compact nature of the Fugu genome. Homology at the amino acid and the nucleotide level with 40% and 51%, respectively, is lower than that of any previously reported Fugu gene. At the level of protein structure, both human and Fugu L1 molecules are composed of six immunoglobulin (Ig)-like domains and five fibronectin (Fn) type III domains, followed by a transmembrane domain and a short cytoplasmic domain. Only the transmembrane and the cytoplasmic domains are significantly conserved in Fugu, supporting their proposed function in intracellular signalling and interaction with cytoskeletal elements in the process of neurite outgrowth and fascicle formation. Our results show that the cytoplasmic domain can be further subdivided into a conserved and a variable region, which may correspond to different functions. Most pathological missense mutations in human L1 affect conserved residues. Fifteen out of 22 reported missense mutations alter amino acids that are identical in both species.

Alternative Splicing↗
PubMed1998

Titles

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Journal Article↗
PubMed1998

Diet and pemphigus. In pursuit of exogenous factors in pemphigus and fogo selvagem.

Individuals with a genetic predisposition to pemphigus will develop the disease only when one or more additional factors are present. The nature of these factors is as yet unknown, but our starting point was that certain drugs (penicillamine, captopril, and rifampicin) are recognized as such factors. Since some nutrients have chemical compositions similar to these known causative drugs, these nutrients may act similarly and, therefore, nutritional factors should also be suspected. As when drugs are involved, elimination of the inciting ingredients may be crucial for management of the disease. This article discusses the possible role of nutritional ingredients in the disease process of pemphigus, including fruit, leaves, roots, seeds, and even water. Possible causative candidates are thiol, thiocyanate, phenols, and tannins.

Diet↗
PubMed1998

Something fishy in the rat brain: molecular genetics of the hypothalamo-neurohypophysial system.

The brain peptides vasopressin and oxytocin play crucial roles in the regulation of salt and water balance. The genes encoding these neurohormones are regulated by cell-specific and physiological cues, but the molecular mechanisms remain obscure. New strategies, involving the introduction of rat transgenes into rats, are being used to address these issues, but the complexity of the rat genome has hampered progress. By contrast, the pufferfish, Fugu rubripes, has a "junk-free" genome. The oxytocin homologue from Fugu, isotocin, has been introduced into rats and is expressed in oxytocin neurons, where it is upregulated by physiological perturbations that upregulate the oxytocin gene. The Fugu and rat lineages separated 400 million years ago, yet the mechanisms that regulate the isotocin and oxytocin genes have been conserved. Fugu genome analysis and transgenesis in the physiologically tractable rat host are a powerful combination that will enable the identification of fundamental components of the neural systems that control homeostasis.

Animals↗
PubMed1998

Biological computation.

It is argued that biological systems can be viewed as special computing devices. This view emerges from considerations of how information is stored in and retrieved from the genes. Genes can only specify the properties of the proteins they code for, and any integrative properties of the system must be 'computed' by their interactions. This provides a framework for analysis by simulation and sets practical bounds on what can be achieved by reductionist models.

Computational Biology↗
PubMed1998

A stage of change approach to addiction in the medical setting.

Despite recent advances in its understanding and treatment, addiction remains a difficult challenge for clinicians within medical settings such as the general hospital. The use of single, traditional paradigms (disciplinary, therapeutic, educational, or libertarian) for approaching addiction-related problems have often failed to embrace the complexity of the patients' motivation to change. Prochaska and DiClemente's [7] stage of change model offers a realistic, practical, and broadly applicable means by which clinicians can facilitate behavioral change from the stage of denial (precontemplation) through that of sustained recovery (maintenance). Clinicians can help addicted individuals to move from precontemplation to contemplation by enhancing their ambivalence; from contemplation to preparation by considering their history of change; from preparation to action by flexibly intervening based on this understanding; and from action to maintenance by evaluating the outcomes of these interventions. A stage of change model is also useful in understanding the process of change in clinicians' own approaches to patients with substance use disorders.

Adult↗
PubMed1998

Different patterns of in vitro acantholysis in normal human skin samples explanted from different sites of the body.

BACKGROUND: The factors that contribute to a preferential anatomic localization of pemphigus lesions are not well known. In particular, the question arises as to whether certain skin areas may be more acantholysis-prone than others. OBJECTIVE: To verify whether, in pemphigus patients, a different susceptibility to acantholysis exists among different cutaneous regions, the technique of tissue cultures was used. METHODS: Normal human skin explants from two distinct anatomic regions (back and buttocks) of two former pemphigus patients were cultured in vitro in the presence of enalapril (6 mM) or cystamine (10 mM), two substances with a proven biochemical acantholytic effect. After 4 days of culture, the tissues were processed for standard histology. RESULTS: Diffuse acantholysis, with large intraepidermal splits, was observed in the explants taken from the backs of both subjects and cultured with either enalapril or cystamine. Mild to moderate acantholytic changes were detected in the explants taken from the buttocks of both subjects and cultured with either enalapril or cystamine. No structural changes were seen in the control cultures. CONCLUSIONS: Pemphigus patients present different thresholds of acantholysis in different areas of their bodies. This might explain, at least in part, certain preferential anatomic localizations of pemphigus lesions.

Acantholysis↗
PubMed1998

Dorfman-Chanarin syndrome: morphologic studies and presentation of new cases.

Dorfman-Chanarin syndrome, or neutral lipid storage disease with ichthyosis, is a rare inherited metabolic disorder characterized by accumulation of neutral lipids in different tissues. Variability in dermatologic severity is not understood. We report two new cases, compare their features with other reported cases, and examine the possible relationship between the severity of the dermatologic condition and lipid accumulation in various types of skin cells. The localization of lipid droplets was determined in various dermal and epidermal cells by light microscopy of epoxy resin semithin sections and electron microscopy in four cases of Dorfman-Chanarin syndrome. Lipid droplets in the dermis were detected in fibroblasts, Schwann cells in both myelinated and unmyelinated nerves, smooth muscle cells, and sweat gland cells, but not in endothelial cells of blood capillaries. The droplets were not surrounded by a membrane. Findings indicate that there is no correlation between the clinical severity of the disease and the microscopic findings.

Adolescent↗
PubMed1998

Contact dermatitis with systemic symptoms from Agave americana.

BACKGROUND: Twelve cases of contact dermatitis provoked by Agave americana are described, 10 with systemic signs and symptoms and 8 with abnormal laboratory results. RESULTS: Patient history revealed a background of intentional exposure among soldiers seeking sick leave. Treatment with oral antihistamines and topical saline compresses resulted in subsidence of the systemic symptoms within 24 h of hospitalization and regression of cutaneous manifestations in 7-10 days. CONCLUSION: The importance that dermatologists be alert to the possibility of self-inflicted contact dermatitis induced by exposure to plants is stressed, especially to A. americana. Systemic signs are not rare accompanying findings with this plant.

Adolescent↗
PubMed1998

Classic Kaposi's sarcoma: low-dose interferon alfa treatment.

BACKGROUND: Classic Kaposi's sarcoma, a rare form of cancer, has no definitive cure. A beneficial effect of low-dose interferon (IFN) alfa was indicated by some case reports. In the present report, we summarize the results of our experience with subcutaneous low-dose IFN alfa treatment of 11 patients with extensive classic Kaposi's sarcoma and review the literature. DESIGN: Eleven patients, 56-96 years old, were treated: 10 men, 1 woman, 3 of whom had an associated malignancy. Subcutaneous injections of IFN alfa were given, starting with 3 million units 5 times a week, and modified according to side effects and response after 2 weeks (2-6 million units, 3-6 times a week). This treatment was continued for 6 months, except for 1 patient who died after 4 months and another who stopped treatment at 4 months due to surgery but was treated again after recurrence. Treatment was continued after 6 months when a partial response was noted, but further improvement was desired (1 patient). RESULTS: In 9 out of the 11 patients, initial response was noted after 3-13 weeks of treatment. This was manifested by a reduction of lesion size and fading of color, leading to a partial resolution. Maximum response was achieved after 4-6 months. Remission lasted 4-72 months. Recurrences were retreated, with additional remissions after only 5-8 weeks of treatment. Side effects included fever and fatigue, which were overcome by dose reduction. CONCLUSION: Whereas in AIDS-related Kaposi's sarcoma patients become refractory to IFN, this was not observed in our patients with classic Kaposi's sarcoma. Moreover, unlike AIDS-related Kaposi's sarcoma, continuous treatment was not needed in classic Kaposi's sarcoma, and recurrences were responsive to retreatment.

Aged↗
PubMed1998

Peeling skin syndrome with hair changes.

A 13-year-old boy with typical peeling skin syndrome (PSS) is described. The clinical picture corresponded to the inflammatory variant of PSS (type B). In addition, the patient had gross and microscopic hair anomalies such as trichorrhexis invaginata-like changes, irregular hair shaft torsions and moniliform hair shaft diameter reductions. The observed dysmorphic hair changes are discussed and interpreted as being an integral component of the dermatosis in this case. To the best of our knowledge, such hair anomalies have not yet been described in PSS.

Adolescent↗
PubMed1998

Identification of an evolutionarily conserved 110 base-pair cis-acting regulatory sequence that governs Wnt-1 expression in the murine neural plate.

The generation of anterior-posterior polarity in the vertebrate brain requires the establishment of regional domains of gene expression at early somite stages. Wnt-1 encodes a signal that is expressed in the developing midbrain and is essential for midbrain and anterior hindbrain development. Previous work identified a 5.5 kilobase region located downstream of the Wnt-1 coding sequence which is necessary and sufficient for Wnt-1 expression in vivo. Using a transgenic mouse reporter assay, we have now identified a 110 base pair regulatory sequence within the 5.5 kilobase enhancer, which is sufficient for expression of a lacZ reporter in the approximate Wnt-1 pattern at neural plate stages. Multimers of this element driving Wnt-1 expression can partially rescue the midbrain-hindbrain phenotype of Wnt-1(-/-) embryos. The possibility that this region represents an evolutionarily conserved regulatory module is suggested by the identification of a highly homologous region located downstream of the wnt-1 gene in the pufferfish (Fugu rubripes). These sequences are capable of appropriate temporal and spatial activation of a reporter gene in the embryonic mouse midbrain; although, later aspects of the Wnt-1 expression pattern are absent. Genetic evidence has implicated Pax transcription factors in the regulation of Wnt-1. Although Pax-2 binds to the 110 base pair murine regulatory element in vitro, the location of the binding sites could not be precisely established and mutation of two putative low affinity sites did not abolish activation of a Wnt-1 reporter transgene in vivo. Thus, it is unlikely that Pax proteins regulate Wnt-1 by direct interactions with this cis-acting regulatory region. Our analysis of the 110 base pair minimal regulatory element suggests that Wnt-1 regulation is complex, involving different regulatory interactions for activation and the later maintenance of transgene expression in the dorsal midbrain and ventral diencephalon, and at the midbrain-hindbrain junction.

Animals↗