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S Prime

Publications and source records attributed to S Prime.

12 recordsLinked to original sources

Signal pathways that transduce growth factor-stimulated mitogenesis in bone cells.

This investigation examined which signal pathways are of relevance in growth factor-stimulated bone cell mitogenesis. Platelet-derived growth factor (PDGF) and insulin-like growth factor-II (IGF-II) were potent mitogens for both the MG-63 osteoblast cell line and for primary cultures of human osteoblasts (HObs). The mitogenic action of both IGF-II and PDGF was attenuated by pertussis toxin (Ptx), by indomethacin, and by the lipoxygenase inhibitors BW755C74 and BW4AC. A combination of Ptx and indomethacin caused much greater inhibition but failed to abolish mitogenesis completely. PDGF significantly elevated inositol phosphates levels in both cell types; IGF-II had no effect on this pathway. In MG-63 cells, we demonstrated tyrosine phosphorylation of high-molecular-weight substrates elicited by both PDGF and IGF-II. Genistein inhibited the phosphorylation and mitogenic response to PDGF, but had no effect on IGF-II-induced tyrosine phosphorylation or mitogenesis. Another inhibitor of tyrosine kinases, methyl 2,5-dihydroxycinnamate, (MDHC), inhibited PDGF-stimulated mitogenesis effectively in both cell types but only blocked IGF-II-induced mitogenesis in MG-63 cells. The specificity of these inhibitors suggests that particular tyrosine kinases may regulate growth factor-induced stimulation of bone cells.

Cell Division↗

Trigeminal neuralgia and multiple sclerosis. A complex diagnosis.

Trigeminal neuralgia is a well-recognized complication in patients with multiple sclerosis. A case report is presented that describes multiple sclerosis in a middle-aged man with otherwise classical unilateral trigeminal neuralgia who demonstrated a variable response to pharmacologic and surgical intervention. The case highlights the difficulties of diagnosis when trigeminal neuralgia occurs concurrently with multiple sclerosis.

Adult↗

Primary biliary cirrhosis. Sole presentation with rampant dental caries.

A 55-year-old woman was referred by her general dental practitioner for management of rampant dental caries of recent onset. Examination revealed a very dry mouth, angular stomatitis, and multiple carious lesions. Labial salivary gland biopsy showed features consistent with Sjögren's syndrome. Hematologic investigations showed antimitochondrial antibodies at a titer of 1 in 320, highly suggestive of primary biliary cirrhosis that was confirmed by liver biopsy.

Autoantibodies↗

Correlated abnormalities of transforming growth factor-beta 1 response and p53 expression in thyroid epithelial cell transformation.

Using the thyroid follicular cell as a model for multi-stage carcinogenesis, we have investigated the role of two potential negative growth regulators ('anti-oncogenes') in epithelial tumour progression--transforming growth factor-beta 1 (TGF beta 1) and p53. Normal follicular cells, as expected, showed marked growth inhibition in response to TGF beta 1. Adenoma cells were equally inhibited. In contrast, spontaneously and SV40-immortalised follicular cell lines showing features of malignant transformation (notably loss of growth factor dependence) had lost all responsiveness to TGF beta 1, accompanied by a partial loss of its receptors. p53 protein was below detectable limits in normal and in adenoma cells but in contrast very high levels were observed in all three transformed lines. In the SV40-immortalised cells, this was expected in view of the known stabilising effect of the viral large T protein. In the spontaneous line we found strong evidence for point mutation of p53, which is known to have the same effect. Both mechanisms result in loss of p53 tumour suppressor function despite increased protein content. We conclude that loss of inhibition by TGF beta and inactivation of p53 are important steps in in vitro immortalisation and/or in vivo tumour progression in human thyroid follicular cells, and speculate that p53 may mediate or be required for the inhibitory signal normally induced by TGF beta 1.

Adenoma↗

Nucleic acid probes in the study of latent viral disease.

Despite the apparent complexities of vocabulary and techniques involved in nucleic acid hybridization, these methods should become important new weapons in the pathologist's armoury. The particular strengths lie in the analysis of genes whose protein products defy detection either because they are absent (due, for example, to cellular controls as found in viral latency), to a point mutation, or to gene deletion (as is often the case with cellular oncogenes). However, the mere application of this technology will not solve all diagnostic problems. One must be aware, particularly in applying in situ hybridization to a new system, of the artefactual binding of the probes, and suitable control and duplicate experiments should be performed. In addition, it is vital to verify the identity of the probes and the specificity of the reaction by filter hybridization. The latter procedure may seem unwieldy, but is, in fact, no more complex than the recommended procedures for immunohistochemistry, as discussed by Matthews (this symposium). Sadly, for both hybridization and immunological detection, operator inexperience has often prevented such checks of specificity and as a result many spurious results populate the scientific literature, for example a recent controversy over the detection of Human T cell Lymphotrophic Virus Type 1 in multiple sclerosis patients. With careful application, however, these techniques will permit the detection of viral molecules under conditions where traditional electron microscopy/histology have failed, and may reveal possible viral aetiologies for a range of hitherto non-viral diseases.

Autoradiography↗

Papillomaviruses: their possible role in oral disease.

Papillomaviruses are ubiquitous DNA viruses that are epitheliotropic and produce a range of epithelial neoplasms, both benign and malignant, in animals and man. Human papillomaviruses are associated with a variety of rare and uncommon oral lesions, and there has been increasing suspicion that they may be implicated also in some premalignant and malignant oral lesions.

Animals↗