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Combined neodymium and strontium isotope studies on Tertiary volcanics from northwest Scotland indicate that their parental mantle isotopic compositions have been substantially modified in many instances by contamination with the Precambrian continental crust through which they were erupted. The occurrence of samarium-neodymium and rubidium-strontium "pseudoisochrons" of different ages in these contaminated continental volcanics indicates that they are artifacts of the contamination processes and have no temporal significance with respect to mantle fractionation events.

The presence of an acyltransferase activity which catalyzes the transfer of palmitic acid from palmitoyl coenzyme A to mucus glycoprotein has been demonstrated in the microsomal fraction of human rectal mucosa. The activity of this enzyme in the mucosa of patients with cystic fibrosis (CF) was found to be 3.5 times higher than that from normal individuals. The CF mucus glycoprotein in comparison to that of normal contained 1.3 times more associated lipids and 6 times more covalently bound fatty acids. The viscosity of the intact CF glycoprotein was 1.8 times higher than that of normal glycoprotein. Extraction of associated lipids led to 3-fold drop in the viscosity of CF glycoprotein and 5-fold drop in the case of normal glycoprotein. Further loss in the viscosity occurred following removal of the covalently bound fatty acids. The viscosity of such modified CF mucus glycoprotein was only about 10% higher than that of similarly treated normal glycoprotein.

1. Alkaline secretion and mucin output were analyzed along the gastrointestinal tract of a dog in response to luminal application of HCl and taurocholate with and without pretreatment with indomethacin. 2. Mucins derived from the different areas displayed similar contents of protein and carbohydrate but differed with respect to associated and covalently bound lipids. 3. Application of HCl or taurocholate in all the regions caused an increase in the output of mucins and HCO3-. However, mucins elaborated in response to HCl exhibited higher total lipid content and were richer in phospholipids. 4. Pretreatment with indomethacin prior to HCl application led to a reduction in HCO3- and caused a decrease in mucin phospholipid content, but had no effect on HCO3- secretion and the lipid content of mucins elaborated in response to taurocholate. 5. The results indicate that mucins elaborated along the gastrointestinal tract differ with respect to lipids, and that their output in response to HCl is mediated by prostaglandins.

The enzymic activity which catalyses transfer of palmitic acid from palmitoyl coenzyme A to mucus glycoprotein was found in Triton X-100 extracts of the microsomal fraction of rat submandibular and sublingual salivary glands. The acyltransferase activity of this fraction was 1.3-1.4 times greater in submandibular gland than in sublingual gland. Further subcellular fractionation of submandibular gland showed that the enzyme activity was associated with a Golgi-rich membrane fraction. Optimum enzyme activity for fatty acylation of mucus glycoprotein was at pH 7.4 using 0.5 per cent Triton X-100, 2 mM dithiothreitol 25 mM NaF and 10 mM MgCl2; higher concentrations were inhibitory. The apparent Km of the submandibular microsomal enzyme for mucus glycoprotein was 5.9 X 10(-7) M, and for palmitoyl-CoA, 3.3 X 10(-5) M. The 14C-labelled glycoprotein product of the reaction co-migrated on CsCl equilibrium, density-gradient centrifugation with submandibular mucus glycoprotein, and contained ester-bound palmitic acid. The fatty acyltransferase showed no activity with proteolytically-degraded glycoprotein; the acceptor capacity of reduced and S-carboxymethylated glycoprotein was only about 10 per cent lower than that of the intact mucus glycoprotein. This suggests that the acylation of salivary mucus glycoprotein with fatty acids occurs at its non-glycosylated, proteolysis-susceptible regions, and that the majority of these fatty acids are linked to the glycoprotein through hydroxyl esters.

Oligosaccharides prepared from glycosaminoglycans (GAGs) including heparin, heparan sulfate, chondroitin sulfates, dermatan sulfate, and keratan sulfate were analyzed using reverse-phase ion-pairing HPLC and ion-exchange HPLC with suppressed conductivity detection. The results were compared with those obtained by strong anion-exchange HPLC using uv detection. These oligosaccharides were first prepared by enzymatically depolymerizing the GAGs with enzymes including heparin lyase (EC 4.2.2.7), heparan sulfate lyase (EC 4.2.2.8), chondroitin ABC lyase (EC 4.2.2.4), and keratan sulfate hydrolase (EC 3.2.1.103). Analysis was then performed without derivitization under isocratic conditions with a limit of sensitivity in the picomole range. Preliminary studies suggest that this approach may be particularly useful in examining oligosaccharides having no uv chromophore such as those prepared from keratan sulfate.

We report 21 cases of stress injury of the distal radial growth plate-occurring in gymnasts before skeletal maturity. The injury appears to be caused by inability of the growth plate to withstand rotational and compressive forces. Our observations have confirmed that the skeletal age of gymnasts is retarded, which increases the length of time during which the epiphysis is at risk of damage.

The coupling of high-performance anion-exchange chromatography with pulsed amperometric detection provides a much needed analytical tool for the analysis of the carbohydrates of glycoconjugates.

The contribution of associated and covalently bound lipids to the viscosity of gastric mucus glycoprotein in healthy and cystic fibrosis (CF) individuals was investigated. While both preparations exhibited similar contents of protein and carbohydrate, the CF glycoprotein contained 1.3 times more associated lipids and 6 times more covalently bound fatty acids. The viscosity of CF mucus glycoprotein was about 1.8 times higher than that of normal glycoprotein. Extraction of associated lipids lead to 3-fold drop in the viscosity of CF glycoprotein and 5-fold drop in the case of normal glycoprotein. Removal of covalently bound fatty acids caused further 1.6-fold reduction in the viscosity of normal mucus glycoprotein and 6-fold in CF glycoprotein. The viscosity of the delipidated and deacylated CF mucus glycoprotein was only about 10% higher than that of the similarly treated normal glycoprotein. The results suggest that the elevated level of covalently bound and associated lipids is responsible for the increased viscosity of CF mucin.

A sulfotransferase activity that catalyzes the transfer of sulfate ester group from 3'-phosphoadenosine 5'-phosphosulfate to carbohydrate chains of gastric mucus glycoprotein has been demonstrated in the antral and body mucosa of rat stomach. Subcellular fractionation studies revealed that the enzyme is associated with Golgi-rich membrane fraction. The sulfotransferase activity of this fraction in antral mucosa was about 35% lower than that in the body. Optimum enzyme activity was obtained with 0.5% Triton X-100 and 30 mM NaF at a pH of 6.8 using desulfated mucus glycoprotein substrate. The enzyme was equally capable of sulfation of the proteolytically degraded and reduced forms of the desulfated glycoprotein, but the acceptor capacity of the intact mucus glycoprotein was about 60% lower than that of the desulfated preparation. The enzyme preparation also catalyzed the transfer of sulfate to galactosylceramide. The sulfation of mucus glycoprotein, however, was not affected by the presence of this glycolipid, suggesting that the sulfotransferase involved in mucus glycoprotein sulfation is different from that responsible for the synthesis of sulfatoglycosphingolipid. The mucus glycoprotein sulfotransferase activity was inhibited by ethanol. The rate of inhibition was proportional to the concentration of ethanol up to 0.3 M and was of the competitive type. The apparent Km value of the enzyme for mucus glycoprotein was 10.5 X 10(-6) M (21 mg/ml), and the KI in the presence of ethanol was 4.7 x 10(-1) M. The 35S-labeled mucus glycoprotein product of the enzyme reaction gave in CsCl density gradient a band in which the 35S label coincided with the glycoprotein. Alkaline borohydride reductive cleavage of this glycoprotein led to the liberation of the label into reduced acidic oligo-saccharide fraction. Most of the label was found incorporated in three oligosaccharides. These were identified as tri-, tetra-, and pentasaccharides, each carrying a labeled sulfate ester group on the terminal N-acetyl-glucosamine residue. Based on the results of structural analyses, the most abundant oligosaccharide was characterized as SO3H----6GlcNAc beta 1----3Gal beta 1----3GalNAc-ol.

A sulfotransferase activity which catalyzes the transfer of a sulfate group from 3'-phosphoadenosine-5'-phosphosulfate to gastric mucus glycoprotein has been demonstrated in the rat gastric mucosa. Subcellular fractionation studies revealed that the enzyme activity was present in a Golgi-rich membrane fraction. Optimum enzymatic activity for sulfation of mucus glycoprotein was obtained with 0.5% Triton X-100 and 30 mM NaF at a pH of 6.8. The apparent Km of the enzyme for gastric mucus glycoprotein was 10.5 microM, and the sulfate ester was found incorporated into the carbohydrate chains of mucin. The sulfo-transferase activity of the Golgi enzyme was stimulated by sofalcone, while reduction in the rate of sulfation occurred in the presence of sucralfate and aspirin. The rate of enhancement of mucin sulfation by sofalcone was proportional to the drug concentration up to 5 X 10(-7) M, at which concentration a 17% increase in the glycoprotein sulfation was attained. The rate of inhibition of mucin sulfation was proportional to concentrations of aspirin up to 3 X 10(-4) M and of sucralfate up to 1 X 10(-4) M, at which concentrations about 50% reduction in sulfotransferase activity was obtained. The apparent KI values calculated from the double-reciprocal plots were 15.1 microM for aspirin and 19.6 microM for sucralfate. The results suggest that although both sucralfate and sofalcone are potent gastric mucosal strengthening agents, only sofalcone is capable of enhancement of the sulfotransferase enzyme involved in gastric mucin sulfation.

In a first experiment, subjects verbalizing the stream of consciousness for a 5-min period were asked to try not to think of a white bear, but to ring a bell in case they did. As indicated both by mentions and by bell rings, they were unable to suppress the thought as instructed. On being asked after this suppression task to think about the white bear for a 5-min period, these subjects showed significantly more tokens of thought about the bear than did subjects who were asked to think about a white bear from the outset. These observations suggest that attempted thought suppression has paradoxical effects as a self-control strategy, perhaps even producing the very obsession or preoccupation that it is directed against. A second experiment replicated these findings and showed that subjects given a specific thought to use as a distracter during suppression were less likely to exhibit later preoccupation with the thought to be suppressed.

The effect of luminal application of arachidonic acid on the alkaline secretion, prostaglandin generation, and mucus glycoprotein output and composition was studied in proximal and distal duodenum of conscious dogs. Surgically prepared duodenal loops were instilled in vivo for up to 2 h with saline (control) followed by various concentrations (12.5-100 micrograms/ml) of arachidonic acid. The experiments were conducted with and without intravenous pretreatment with indomethacin. The recovered instillates were assayed for the content of prostaglandin and HCO3-, and used for the isolation of mucus glycoprotein. Exposure of duodenal mucosa to arachidonic acid led to concentration-dependent increase in the output of HCO3- and prostaglandin generation. In both cases this response was greater in the proximal duodenum. Pretreatment with indomethacin caused reduction in the basal HCO3- and prostaglandin output, and prevented the increments evoked by arachidonic acid. The proximal and distal duodenum displayed similar basal output and composition of mucus glycoprotein. Comparable increases in these glycoproteins were also obtained with arachidonic acid, the effect of which was abolished by indomethacin. Compared to basal conditions, mucus glycoproteins elaborated in response to arachidonic acid exhibited higher contents of associated lipids and covalently bound fatty acids, and contained less protein. The associated lipids of mucus glycoproteins elaborated in the presence of arachidonic acid showed enrichment in phospholipids and decrease in neutral lipids. The carbohydrate components in these glycoproteins also exhibited higher proportions of sialic acid and sulfate. The changes brought about by arachidonic acid were prevented by indomethacin pretreatment, and in both cases the glycoprotein composition returned to that obtained under basal conditions. The enrichment of mucus glycoprotein in lipids, sialic acid and sulfate in response to endogenous prostaglandin may be of significance to the function of this glycoprotein in the hostile environment of the duodenum.