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Biomedical subjects

W G Taylor

Publications and source records attributed to W G Taylor.

At least 37 records · Page 2Linked to original sources

Keratinocyte growth factor.

Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family (FGF-7) with a distinctive pattern of target-cell specificity. Studies performed in cell culture suggested that KGF was mitogenically active only on epithelial cells, albeit from a variety of tissues. In contrast, KGF was produced solely by cells of mesenchymal origin, leading to the hypothesis that it might function as a paracrine mediator of mesenchymal-epithelial communication. Biochemical analysis and molecular cloning established that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2 gene. Many detailed investigations of KGF and KGFR expression in whole tissue and cell lines largely substantiated the pattern initially perceived in vitro of mesenchymal and epithelial distribution, respectively. Moreover, functional assays in organ culture and in vivo and studies of KGF regulation by sex steroid hormones reinforced the idea that KGF acts predominantly on epithelial cells to elicit a variety of responses including proliferation, migration and morphogenesis.

Animals↗

Metabolites of N-ethylbenzamide, N,N-diethylbenzamide and related compounds detected in rat urine by NMR spectroscopy.

In rats treated ip with N-ethylbenzamide (EB) at doses of 250-500 mg/kg, this amide was metabolized by hydrolysis to ethylamine and benzoic acid, the latter detected in the urine as hippuric acid. Proposed metabolic pathways were investigated by treatment of male Wistar rats with EB and N-ethyl-alpha-13C-benzamide followed by examination of urine samples by high-resolution NMR spectroscopy. Ethylamine was detected by 1H and 13C NMR techniques. Estimation of metabolite levels in 24-hr posttreatment urine by 1H NMR spectroscopy with an internal standard of 3-(trimethylsilyl)-1-propanesulfonic acid and correction for background levels of hippuric acid in control urine showed that the percentage of the dose excreted as hippuric acid was 52-76%. The corresponding range for the excretion of ethylamine (detected as an ethylammonium cation) was 27-41%. Signals for EB, benzamide, and benzoic acid were not above the background in urine of treated animals. A similar NMR study with unlabeled p-chloro-N-ethylbenzamide (p-Cl EB) resulted in the detection of p-chlorohippuric acid and ethylamine. Treatment of rats with N,N-diethylbenzamide and p-chloro-N,N-diethylbenzamide gave the same detectable metabolites in the urine as those found in experiments with EB and p-Cl EB. These observations could be rationalized with a metabolic pathway involving an initial oxidative mono-N-deethylation reaction followed by enzymatic hydrolysis of the secondary amides to ethylamine and benzoic acids and conjugation of the latter with glycine. N-Methylbenzamide was also found to be eliminated in the urine as hippuric acid.

Animals↗

Thin-layer chromatographic detection of ivermectin in cattle serum.

A study was conducted on the detection of ivermectin (22,23-dihydroavermectin B1) in cattle serum by thin-layer chromatography (TLC) after derivatization of this parasiticide by the known reaction with trifluoroacetic anhydride-1-methylimidazole and visual examination of the chromatograms under long-wavelength ultraviolet light. By derivatization of reference samples of ivermectin in acetonitrile, approximately 0.1 ng of a highly fluorescent material, tentatively identified as 2,5,6-tetradehydro-5,7-dideoxy-22,23-dihydroavermectin B1, could be detected on silica-gel thin layer plates. Extraction of fortified serum samples with methyl tert.-butyl ether followed by derivatization, hydrolysis, partitioning between water-hexane and TLC gave a limit of detection of 1-2 ng/ml. With these simple techniques ivermectin could be detected in cattle serum for 3-4 weeks after subcutaneous treatment of Hereford heifers.

Animals↗

Antenatal assessment of neurological impairment.

An unreactive cardiotocograph late in the mid-trimester led to a sequence of investigations that revealed an appropriately grown fetus, with hepatic calcification, and evidence of intrauterine infection. Ultrasound observation and stimulation of the fetus with vibration and glucose revealed altered neurophysiological responses. The profound neurological impairment was confirmed by detailed neonatal investigations.

Adult↗

Pharmacokinetics of phenolsulfonphthalein in sheep.

Pharmacokinetic variables of phenolsulfonphthalein (PSP) were determined in sheep after rapid IV injection and IV infusion to steady state. In Suffolk wethers, an average of < 75% of an IV administered dose was eliminated in urine, indicating that measures of systemic clearance overestimate renal clearance in this species. Furthermore, PSP elimination from plasma was more rapid in Suffolk than Rambouillet wethers and, in Suffolk ewes, systemic clearance decreased from mean +/- SD 7.8 +/- 0.3 ml/min/kg of body weight to 4.7 +/- 1.1 ml/min/kg at steady-state plasma concentration of 2.4 +/- 0.3 and 151.3 +/- 31.8 micrograms/ml, respectively. These observations indicate that, similar to that in other species, systemic clearance of PSP in sheep is concentration-dependent and that significant differences may exist between breeds.

Animals↗

Processing of hepatocyte growth factor to the heterodimeric form is required for biological activity.

Hepatocyte growth factor is a plasminogen-like molecule with diverse biological effects. Although it is synthesized as a single chain polypeptide, it was originally purified as a disulfide-linked heterodimer which was generated by an internal proteolytic event. Subsequent work indicated that preparations consisting largely of the monomeric form also exhibited potent activity. By using a combination of protease inhibition and site-directed mutagenesis, we established that conversion of the single chain polypeptide to the heterodimer occurred during the bioassay and was required for mitogenic and motogenic activity.

Animals↗

Efficacy of a porcelain refinishing system in restoring surface finish after grinding with fine and extra-fine diamond burs.

Commercial porcelain refinishing kits are claimed to restore the surface finish on porcelain after adjustments in circumstances that preclude reglazing. This study investigates the efficacy of one such kit in restoring a Vitadur N porcelain surface finish after grinding with fine (30 microns grit-red band) and extra-fine (15 microns grit-yellow band) high-speed diamond burs. The production of the porcelain test samples, the refinishing procedures, and the refinishing times were standardized throughout. Techniques were selected to simulate clinical practice. Randomly selected examples of surfaces created during refinishing were subjected to scanning electron microscopy, using standard kV and tilt angle settings, and to surface profilometry tracings. Roughness average (Ra) readings were recorded for each test specimen for every surface finish. Ra readings were analyzed statistically using a two-way unbalanced model for analysis of variance. Although refinishing after grinding with a 15 microns grit bur produced surfaces significantly smoother than on specimens previously ground with the 30 microns grit burs, the surfaces remained significantly rougher than when originally glazed. It is concluded that, using the type of kit tested, burs of a grade finer than the existing 15 microns grit yellow band types would be appropriate for porcelain adjustments to permit subsequent refinishing to a surface smoothness comparable to the original glaze.

Aluminum Oxide↗

Effect of impression tray design upon the accuracy of stone casts produced from a single-phase medium-bodied polyvinyl siloxane impression material.

The study examined the accuracy of stone casts produced from impressions taken in stock polycarbonate trays, some of which had been strengthened with autopolymerizing polymethyl methacrylate resin and four designs of custom-made trays. Impressions of an acrylic master model of the mandibular arch on which two extracoronal crown preparations and one intracoronal inlay preparation had been carried out were taken using a medium-bodied polyvinyl siloxane material. Each preparation had been intended with a reference point for later measurement. Five impressions were taken for each type of tray and these were cast in die-stone after 24 h. The distances between the points were measured with a reflex microscope and the means determined for each design of tray. The mean difference between casts produced from the various tray designs and the acrylic master model were determined for each of the distances between the three measuring points. Statistical analysis showed that, with the stock trays, there were no significant differences between any of the modifications, or between them and the acrylic model, for any of the three distances (P greater than 0.1). When the results from the custom-made trays were analysed there were statistical differences between the acrylic model and the casts from the unperforated tray with no stops (P = 0.02), and between the unperforated tray with no stops and the perforated with stops for the distance A-B (P less than 0.01). There were no other significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Dental Impression Materials↗

A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor.

A heparin-binding mitogen was isolated from conditioned medium of human embryonic lung fibroblasts. It exhibited broad target-cell specificity whose pattern was distinct from that of any known growth factor. It rapidly stimulated tyrosine phosphorylation of a 145-kDa protein in responsive cells, suggesting that its signaling pathways involved activation of a tyrosine kinase. Purification identified a major polypeptide with an apparent molecular mass of 87 kDa under reducing conditions. Partial amino acid sequence analysis and cDNA cloning revealed that it was a variant of hepatocyte growth factor, a mitogen thought to be specific for hepatic cells and structurally related to plasminogen. Recombinant expression of the cDNA in COS-1 cells established that it encoded the purified growth factor. Its site of synthesis and spectrum of targets imply that this growth factor may play an important role as a paracrine mediator of the proliferation of melanocytes and endothelial cells, as well as cells of epithelial origin.

Amino Acid Sequence↗

Refinishing of porcelain by using a refinishing kit.

Dental porcelain occasionally requires adjustment in circumstances that preclude reglazing. Porcelain refinishing kits are now available commercially. The effects of using one such kit on Vita VMK bonded porcelain was investigated qualitatively and quantitatively using scanning electron microscopic and surface profilometric techniques, respectively. The kit proved incapable of restoring a surface glaze to porcelain adjusted using a fine (red band) diamond bur, but was capable of reducing significantly the surface roughness (Ra) of adjusted porcelain. The importance of distinguishing between the integrity of the surface glaze and measurements of surface roughness is discussed. Confining the application of refinishing procedures to the surface adjusted is important to avoid unnecessary removal of the original surface glaze.

Carbon↗

Effect of impression tray design and impression technique upon the accuracy of stone casts produced from a putty-wash polyvinyl siloxane impression material.

This study examined the accuracy of stone casts produced from impressions taken in stock polycarbonate trays, some of which had been strengthened with autopolymerizing polymethyl methacrylate resin. Three techniques were used to make the impression of an acrylic master model of the mandibular arch on which two extracoronal preparations for bridgework and one intracoronal inlay preparation had been carried out. Each preparation had been indented with a reference point for later measurement. The impression material was a putty-wash polyvinyl siloxane material. Five impressions were taken for each type of tray for each impression technique and these were cast in die-stone after 24 h. The distances between the points were measured with a reflex microscope and the means determined for each design of tray. The mean difference between casts produced from the various tray designs and the acrylic master model were determined for each of the distances between the three measuring points for the various impression techniques. Statistical analysis showed that, with the polycarbonate stock trays, there were significant differences between some of the modifications and between them and the acrylic model, for the three distances (P less than 0.05). These differences were limited to one measurement for one design of tray for each of the two-stage impression methods. With the one-stage technique the unreinforced tray and those reinforced with acrylic, over the heels and anteriorly, and the barred design were statistically significantly different from the acrylic model for measurement A-B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesives↗

Comparison of biological and immunochemical properties indicates that scatter factor and hepatocyte growth factor are indistinguishable.

Scatter factor, a stimulant of epithelial cell motility, and Hepatocyte Growth Factor (HGF) were compared by cross-biological studies using naturally occurring and recombinant proteins in four bioassays. Both scatter factor and HGF produced similar effects in cell motility and DNA synthesis assays. Antibodies to scatter factor or HGF neutralized the biological activities of each cytokine, and in immunoblotting reacted with species of the same Mr. These results, together with the available sequence data, suggest that scatter factor and HGF are the same protein.

3T3 Cells↗

EGF receptor and erbB-2 tyrosine kinase domains confer cell specificity for mitogenic signaling.

The epidermal growth factor (EGF) receptor (EGFR) can efficiently couple with mitogenic signaling pathways when it is transfected into interleukin-3 (IL-3)-dependent 32D hematopoietic cells. When expression vectors for erbB-2, which is structurally related to EGFR, or its truncated counterpart, delta NerbB-2, were introduced into 32D cells, neither was capable of inducing proliferation. This was despite overexpression and constitutive tyrosine kinase activity of their products at levels associated with potent transformation of fibroblast target cells. Thus, EGFR and erbB-2 couple with distinct mitogenic signaling pathways. The region responsible for the specificity of intracellular signal transduction was localized to a 270-amino acid stretch encompassing their respective tyrosine kinase domains. Thus, tissue- or cell-specific regulation of growth factor receptor signaling can occur at a point after the initial interaction of growth factor with receptor. Such specificity in signal transduction may account for the selection of certain oncogenes in some malignancies.

Animals↗

Growth factor-regulated pathways in epithelial cell proliferation.

Investigations of the pathways regulating normal growth of epithelial cells have revealed the existence of two major growth-factor signaling cascades required for proliferation. One pathway is activated by IGF-1 or high insulin concentration. The other is triggered by EGF, TGF alpha, or members of the FGF family, including the recently discovered epithelial-cell-specific growth factor, designated keratinocyte growth factor (KGF). Its expression pattern in vivo suggests that KGF plays an important normal physiologic role as a stromal effector of epithelial cell proliferation. Oncogenes, which represent constitutively activated forms of genes critically involved in growth-factor signaling pathways, specifically abrogate the requirement for mitogens of the EGF pathway. Examples of such genes include the erbB/EGF receptor and erbB-2, which encode structurally related receptor proteins and are often amplified and/or overexpressed in epithelial malignancies. Employing reduced stringency hybridization with v-erbB as a probe, we recently identified a third member of this receptor family, designated erbB-3. cDNA cloning revealed a predicted 148-kD transmembrane polypeptide with structural features similar to those of the EGF receptor. Normal erbB-3 expression in keratinocytes and glandular epithelium suggests its physiologic role in these cell types. Moreover, markedly elevated erbB-3 mRNA levels in certain mammary tumor cell lines suggest that increased erbB-3 expression may also play a role in some human epithelial malignancies.

Animals↗