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W J Griffiths

Publications and source records attributed to W J Griffiths.

At least 55 records · Page 3Linked to original sources

Electrospray-collision-induced dissociation mass spectrometry of mono-, di- and tri-hydroxylated lipoxygenase products, including leukotrienes of the B-series and lipoxins.

Collision-induced dissociation (CID) mass spectra were recorded on underivatized, hydroxylated lipoxygenase products, including S(S)-, 12(S)- and 15(S)-hydroxyeicosatetraenoic adds (HETE), leukotriene (LT) B4, LTB5, the LTB4 metabolites 20-OH-LTB4, 20-COOH-LTB4 and 10,11-dihydro-LTB4, the LTB4 isomers 6-trans-LTB4, 6-trans,12-epi-LTB4 and S(S),12(S)-dihydroxyeicosatetraenoic acid (diHETE) as well as S(S),6(R)-diHETE, 14(S), 15(R)-diHETE and lipoxin (LX) A4 and B4. Pseudomolecular [M-H]- parent ions were generated by electrospray ionization. The ions were accelerated to 4 keV, selected by the double focusing sectors Of 2 hybrid tandem mass spectrometer, decelerated to 400 eV and focused into a collision cell containing xenon. The resulting fragment ions were mass analysed by an orthogonal time-of-flight analyser. The CID spectra obtained were structurally informative allowing isomer differentiation.

Blood Platelets↗

The identification of novel steroid N-acetylglucosaminides in the urine of pregnant women.

A series of pregnanediols and pregnanetriols doubly conjugated with N-acetylglucosamine and glucuronic or sulfuric acid has been identified in urine from pregnant women. Steroid conjugates were separated by ion-exchange chromatography and the glucuronide and monosulfate fractions were analysed by fast atom bombardment mass spectrometry. After removal of the acid moiety, the neutral steroids were isolated, derivatized, and analysed by gas chromatography-mass spectrometry (GC-MS). The analyses revealed the presence of steroids conjugated with N-acetylhexosamine both in the glucuronide and the monosulfate fractions. Following enzyme hydrolysis, the sugar was identified by GC-MS as N-acetylglucosamine (GlcNAc). The major steroid conjugated with GlcNAc both in the glucuronide and monosulfate fractions was identified as 5alpha-pregnane-3alpha,20alpha-diol. 5beta-Pregnane-3alpha,2Oalpha-diol was also present as a GlcNAc conjugate in both fractions whereas a GlcNAc conjugate of 5alpha-pregnane-3beta,20alpha-diol was only found in the sulfate fraction. 5alpha-Pregnane-3alpha,20alpha,21-triol was a double conjugate with GlcNAc in the sulfate fraction whereas a pregnane-2,3,20-triol was a double conjugate in the glucuronide fraction. The positions of conjugation were determined by collision-induced dissociation of the pseudomolecular anions produced by fast atom bombardment ionization. The sulfate and glucuronic acid moieties were located at C-3 and N-acetylglucosamine at C-20. An alternative localization of GlcNAc at C-21 of 5alpha-pregnane-3alpha,20alpha,21-triol cannot be excluded. Judging from the enzymatic hydrolysis of the conjugates, the sugar was attached in beta-glycosidic linkage. The mean excretion of N-acetylglucosaminides of the pregnanediols and pregnanetriols was 32.2 micromol/g creatinine (range 17.9-49.1 micromol) in five healthy women in the 38th-39th week of pregnancy. The mean excretion of 5beta-pregnane-3alpha,20alpha-diol glucuronide in the same women was 71 micromol/g creatinine, (range 27-127 micromol). This indicates that conjugation with N-acetylglucosamine constitutes a quantitatively important pathway of progesterone metabolism in human pregnancy.

Acetylglucosamine↗

Liquid chromatography/mass spectrometry with collision-induced dissociation of arachidonic acid metabolites derivatized with aminobenzenesulphonic acid.

A fused-silica capillary high-performance liquid chromatography column (i.d. 0.25 mm) packed with octadecylsilane-bonded silica has been used on-line with continuous-flow negative-ion fast-atom bombardment (FAB) mass spectrometry for the separation and structural analysis of series of fatty acids and arachidonic acid metabolites derivatized with 4-aminobenzenesulphonic acid. Negative-ion FAB spectra of the derivatized lipids showed strong [M-H] pseudomolecular ions. Collision-induced dissociation of these anions produced structurally informative daughter ions, arising from charge-remote fragmentations.

Arachidonic Acids↗

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Alcoholism↗

The major metabolites of ursodeoxycholic acid in human urine are conjugated with N-acetylglucosamine.

Ursodeoxycholic acid (750 mg/day) was administered orally to ten healthy subjects over a period of 10 days; 24 hr urine samples were collected the day before and on the last day of the study. Urinary bile acids were extracted, separated into groups of conjugates and analyzed by gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry. Excretion of ursodeoxycholic acid rose from 70 to 2,915 micrograms/24 h. The highest increase was observed among N-acetylglucosamine conjugates, 90% of which constituted the previously unknown double conjugate of ursodeoxycholic acid with N-acetylglucosamine and glycine. Excretion of isoursodeoxycholic acid increased from 50 to 738 micrograms/24 h. This isomerization product of ursodeoxycholic acid was excreted almost exclusively as N-acetylglucosamine conjugate. In total, N-acetylglucosamine conjugates constituted 50% of urinary metabolites of ursodeoxycholic acid. In addition, metabolites of ursodeoxycholic acid hydroxylated at carbon atoms 1, 6, 22 and possibly 21 were observed. These compounds were also found as conjugates with N-acetylglucosamine. Their formation from ursodeoxycholic acid was definitely demonstrated by 13C-labeling after giving [24-13C]ursodeoxycholic acid to one of the healthy subjects and to a patient with extrahepatic cholestasis in whom hydroxylation of ursodeoxycholic acid at C-23 was also observed. The patient was also found to excrete the double conjugate of ursodeoxycholic acid with N-acetylglucosamine and taurine. The N-acetylglucosaminidation of ursodeoxycholic acid in vivo was shown to occur at C-7.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosamine↗

Charge-remote fragmentation of peptides derivatized with 4-aminonaphthalenesulphonic acid.

A series of small peptides has been studied by negative-ion fast-atom bombardment mass spectrometry with collision-induced dissociation. It has been found that by derivatizing peptides with 4-aminonaphthalenesulphonic acid in a peptide linkage at the C-terminus, negative-ion formation can be enhanced and fragmentation in collision-induced dissociation reactions controlled. The peptide-naphthalenesulphonates show charge-remote fragmentations and the resultant spectra give sequence information.

Amino Acid Sequence↗

Positions of conjugation of bile acids with glucose and N-acetylglucosamine in vitro.

In order to establish the position of conjugation of bile acids with glucose or N-acetylglucosamine, glucosides of chenodeoxycholic and hyodeoxycholic acids and of 13C-labeled cholic, lithocholic, chenodeoxycholic, hyodeoxycholic, and ursodeoxycholic acids, and N-acetylglucosaminides of ursodeoxycholic, isoursodeoxycholic, 3-dehydro-ursodeoxycholic, and ursodeoxycholylglycine were synthesized in vitro. The conjugates were purified by anion-exchange chromatography and reversed-phase HLPC and were analyzed by gas chromatography-mass spectrometry. The glucosides of chenodeoxycholic and hyodeoxycholic acids were also analyzed after periodate and chronic acid oxidation. All conjugates were analyzed by fast atom bombardment mass spectrometry with collision-induced dissociation. Glucose conjugation was shown to occur at C-3 in all bile acid glucosides studied. In contrast, the selective N-acetylglucosaminidation of 7 beta-hydroxy bile acids was shown to occur at the 7 beta-position.

Acetylglucosamine↗

Derivatization of bile acids with taurine for analysis by fast atom bombardment mass spectrometry with collision-induced fragmentation.

When analyzed by fast atom bombardment mass spectrometry, taurine-conjugated bile acids give intense [M-H]-pseudomolecular ions that can be subjected to collision-induced fragmentation to give structural information. A method has been developed that permits rapid coupling of taurine to unconjugated, glycine-conjugated, sulfated, and glucuronidated bile acids. The reaction is performed for 2 h at room temperature in aqueous pyridine hydrochloride buffer, with or without dioxane, using 0.1 M 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as the coupling agent and 0.2 M taurine. The yields are higher than 95%. In contrast to published coupling reactions, the method permits conjugation of bile acids with the labile 7 alpha-hydroxy-3-oxo-4-ene structure.

Bile Acids and Salts↗

Charge-remote fragmentation of taurine-conjugated bile acids.

Taurine-conjugated bile acids are an important group of biological metabolites. When investigated by negative-ion fast-atom bombardment collision-induced dissociation mass spectroscopy they show charge-remote fragmentations of the [M-H]- pseudomolecular ion. These fragmentations provide information on the positions of ring substituents remote from the charge site. In the present work we have compared the negative-ion fast-atom bombardment collision-induced dissociation spectra of six different conjugated bile acids.

Bile Acids and Salts↗

Bacteremia associated with esophageal dilatation.

The present study was undertaken because the previously reported incidence of bacteremia associated with esophageal dilatation seemed high, and did not correlate well with clinical experience. Seventeen adult patients were dilated for benign esophageal strictures with one to three dilators on 41 occasions. Five blood cultures were taken over the 30-minute period after each dilatation. Either routinely sterilized dilators or dilators resterilized just before the procedure were used in a random fashion. On 22 of the occasions that routinely sterilized dilators were used in 17 patients, temperatures, white blood counts, and blood cultures were normal in each instance. Resterilized dilators were used on 19 occasions in 15 subjects, and postdilation temperatures and white blood counts were also normal. Two blood cultures from different patients grew Staphylococcus epidermidis, which were felt to be contaminants. On the basis of this and previous studies, extra precautions do not appear to be necessary for dilatation of routine benign strictures. In patients at risk for endocarditis, or those with cancer or tight strictures, it seems advisable to sterilize dilators just before use, and take extra precautions.

Adult↗

Effect of psyllium hydrophilic mucilloid on oral glucose tolerance and breath hydrogen in postgastrectomy patients.

Twenty postgastrectomy patients ingested glucose solutions with or without psyllium hydrophilic mucilloid to determine its effects on their blood glucose and breath hydrogen excretion. On the basis of the breath hydrogen tests following glucose alone, 15 had various degrees of glucose malabsorption which the addition of psyllium markedly reduced. In all 20 patients, psyllium significantly lowered peak blood glucose and prolonged its rate of fall. However, areas under the glucose concentration time curves were similar with and without psyllium, suggesting that total glucose absorption was unaltered by psyllium. In vitro, centrifuged psyllium-water-glucose slurries released glucose over 3 hr into water. Although the mechanisms of the psyllium alteration of the blood glucose and breath hydrogen responses are probably multifactorial, our studies suggest that release from the psyllium-glucose slurry results in a slower and more complete glucose absorption.

Adult↗

Endoscopic cultures of the proximal gastrointestinal tract.

The purpose of this study was to evaluate two methods of obtaining culture material under direct visualization through a fiberoptic upper gastrointestinal endoscope. Collections were made both with a wash pipe and a sterile brush through a sterilized Olympus D panendoscope. Paired aspirate collections were made on 20 occasions from 10 postgastrectomy and six nonoperated patients. Significant bacterial overgrowth was identified equally well by both methods, the the wash tube, which can be reused, is cheaper. The endoscopic method for collecting proximal fluid for culture is simple and can be performed during a routine endoscopy.

Aged↗

Breath hydrogen test after oral lactose in postgastrectomy patients.

The purpose of this study was to compare breath hydrogen tests after oral lactose ingestion in nonoperated subjects and postgastrectomy patients. Simultaneous oral lactose tolerance tests and breath hydrogen tests were performed in 50 subjects. Twenty of the 30 subjects without prior gastric surgery had normal lactase activities and low breath hydrogen concentrations. The other 10 subjects had low lactase levels and increased breath hydrogen concentrations. The remaining 20 subjects had prior gastric surgery. Seven of these had normal lactase activities, no history of milk intolerance and low breath hydrogen concentrations. Two of the postgastrectomy patients had low intestinal lactases, milk intolerance, and high breath hydrogens. The remaining 11 postgastrectomy patients had normal intestinal lactases but high breath hydrogens. Eight of the 11 had milk intolerance while two of the other three had not consumed milk since childhood. From these studies the following conclusions can be reached: 1)a low lactose breath hydrogen test in the postgastrectomy subject correctly identifies the individual with normal lactase activity. However, high breath hydrogen responses, may be found in either those with lactase deficiency or normal lactase activity. 2) Lactose malabsorption would appear to explain the milk intolerance in the postgastrectomy patient with normal lactase activity.

Animals↗

The visible vessel as an indicator of uncontrolled or recurrent gastrointestinal hemorrhage.

Although endoscopic examination in patients with bleeding of the upper gastrointestinal tract has improved diagnostic accuracy, it has not been useful in predicting clinical outcome and has not been shown to improve the patients' prognoses. This article describes a subgroup of patients with acute upper gastrointestinal bleeding whose clinical outcome can be predicted at the time of endoscopy. In 28 of 317 patients who underwent endoscopy, a "visible vessel" was seen in an ulcer presumed to be the bleeding site. All 28 were later recommended for operation because of recurrent (86 per cent) or uncontrolled (14 per cent) hemorrhage. In contrast, 75 per cent of the remaining 289 patients in whom vessels were not seen, whether or not bleeding from ulcers, had single bleeding episodes managed medically. Since patients with a "visible vessel" can be expected to have uncontrolled or recurrent hemorrhage, surgical treatment should be considered at the time of endoscopy if such a vessel is seen.

Acute Disease↗

Nocturnal levels of growth hormone in hyperactive children of small stature.

Growth disturbances have been demonstrated in hyperactive children treated with stimulant medication. This study examines sleep related growth hormone secretion in patients with hyperactive syndrome and relative short stature. Five such patients were compared with 9 age matched controls. There were no differences in sleep patterns, and growth hormone levels for the hyperactive children were within normal limits. This study suggests that hyperactive children with short stature have normal sleep patterns and normal sleep related growth hormone secretion.

Body Height↗