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Biomedical subjects

W Sabbagh

Publications and source records attributed to W Sabbagh.

12 recordsLinked to original sources
PubMed2001

Specificity of MAP kinase signaling in yeast differentiation involves transient versus sustained MAPK activation.

Signals transmitted by common components often elicit distinct (yet appropriate) outcomes. In yeast, two developmental options-mating and invasive growth-are both regulated by the same MAP kinase cascade. Specificity has been thought to result from specialized roles for the two MAP kinases, Kss1 and Fus3, and because Fus3 prevents Kss1 from gaining access to the mating pathway. Kss1 has been thought to participate in mating only when Fus3 is absent. Instead, we show that Kss1 is rapidly phosphorylated and potently activated by mating pheromone in wild-type cells, and that this is required for normal pheromone-induced gene expression. Signal identity is apparently maintained because active Fus3 limits the extent of Kss1 activation, thereby preventing inappropriate signal crossover.

Cell Differentiation↗
PubMed2001

Long-term results of digital arthrodesis with the Harrison-Nicolle peg.

This study determined the long-term success of digital arthrodesis with the Harrison-Nicolle peg. We reviewed 90 digital joints in 60 patients fused with the peg between 1986 and 1998 at a mean follow-up of 6 (range 2-11) years. The prime indication for surgery was rheumatoid arthritis. The early complication rate was 8%. At 1 month 89% of joints were pain-free and stable. In the long-term follow up, 96% of the joints were pain-free and stable, with the original angle of fusion. 85% achieved bony fusion, with no clinical difference between bony and fibrous fusion. Overall there was a significantly higher complication rate in the distal interphalangeal joint. We conclude that, with the exception of the distal interphalangeal joint, the Harrison-Nicolle peg is extremely effective for digital arthrodesis in the rheumatoid patient.

Adult↗
PubMed1998

SXR, a novel steroid and xenobiotic-sensing nuclear receptor.

An important requirement for physiologic homeostasis is the detoxification and removal of endogenous hormones and xenobiotic compounds with biological activity. Much of the detoxification is performed by cytochrome P-450 enzymes, many of which have broad substrate specificity and are inducible by hundreds of different compounds, including steroids. The ingestion of dietary steroids and lipids induces the same enzymes; therefore, they would appear to be integrated into a coordinated metabolic pathway. Instead of possessing hundreds of receptors, one for each inducing compound, we propose the existence of a few broad specificity, low-affinity sensing receptors that would monitor aggregate levels of inducers to trigger production of metabolizing enzymes. In support of this model, we have isolated a novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), which activates transcription in response to a diversity of natural and synthetic compounds. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P-450 genes and is expressed in tissues in which these catabolic enzymes are expressed. These results strongly support the steroid sensor hypothesis and suggest that broad specificity sensing receptors may represent a novel branch of the nuclear receptor superfamily.

Amino Acid Sequence↗
PubMed1998

Pitx2 determines left-right asymmetry of internal organs in vertebrates.

The handedness of visceral organs is conserved among vertebrates and is regulated by asymmetric signals relayed by molecules such as Shh, Nodal and activin. The gene Pitx2 is expressed in the left lateral plate mesoderm and, subsequently, in the left heart and gut of mouse, chick and Xenopus embryos. Misexpression of Shh and Nodal induces Pitx2 expression, whereas inhibition of activin signalling blocks it. Misexpression of Pitx2 alters the relative position of organs and the direction of body rotation in chick and Xenopus embryos. Changes in Pitx2 expression are evident in mouse mutants with laterality defects. Thus, Pitx2 seems to serve as a critical downstream transcription target that mediates left-right asymmetry in vertebrates.

Activin Receptors, Type II↗
PubMed1998

In vitro assessment of a collagen sponge for engineering urothelial grafts.

OBJECTIVE: To investigate the deposition of urinary crystals and the growth characteristics of urothelial cells on a collagen sponge, as a preliminary step in engineering urothelial autologous grafts. MATERIALS AND METHODS: Collagen sponges were exposed to a continuous flow of urine at pH 5.3 and 6.3 for 1 week. The sponges were examined microscopically for crystal deposition and analysed for their calcium content. Two cell lines, RT112, derived from a well-differentiated transitional cell carcinoma, and UROtsa, an immortalized urothelial cell line, were seeded on the collagen sponges. Cells were cultured for 6, 12 and 21 days. The pattern of growth was analysed by histology and immunostaining with a pan-cytokeratin antibody. Growth was assayed to quantify cell proliferation on the sponges. RESULTS: No crystals were evident on any of the collagen sponges. Calcium deposition was negligible at pH 5.3. Although calcium levels were measurable at pH 6.3, the levels were very low. Both cell lines attached and grew in a stratified manner on the collagen sponge, RT112 forming a layer 6-8 cells thick, and UROtsa a layer 4-6 cells thick; cell proliferation was maximal at 5-10 days. The sponge remained easy to handle after 3 weeks in culture. CONCLUSION: These findings show that collagen sponges support the growth and stratification of urothelial cells, and indicate that the collagen sponge is a suitable substrate for developing urothelial autologous grafts.

Calcium↗