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L J O'Donnell

Publications and source records attributed to L J O'Donnell.

At least 19 recordsLinked to original sources
PubMed2006

A method for clustering white matter fiber tracts.

BACKGROUND/PURPOSE: Despite its potential for visualizing white matter fiber tracts in vivo, diffusion tensor tractography has found only limited applications in clinical research in which specific anatomic connections between distant regions need to be evaluated. We introduce a robust method for fiber clustering that guides the separation of anatomically distinct fiber tracts and enables further estimation of anatomic connectivity between distant brain regions. METHODS: Line scanning diffusion tensor images (LSDTI) were acquired on a 1.5T magnet. Regions of interest for several anatomically distinct fiber tracts were manually drawn; then, white matter tractography was performed by using the Runge-Kutta method to interpolate paths (fiber traces) following the major directions of diffusion, in which traces were seeded only within the defined regions of interest. Next, a fully automatic procedure was applied to fiber traces, grouping them according to a pairwise similarity function that takes into account the shapes of the fibers and their spatial locations. RESULTS: We demonstrated the ability of the clustering algorithm to separate several fiber tracts which are otherwise difficult to define (left and right fornix, uncinate fasciculus and inferior occipitofrontal fasciculus, and corpus callosum fibers). CONCLUSION: This method successfully delineates fiber tracts that can be further analyzed for clinical research purposes. Hypotheses regarding specific fiber connections and their abnormalities in various neuropsychiatric disorders can now be tested.

Adolescent↗
PubMed2003

24-hour secretion patterns of plasma oestradiol 17beta in pony mares in late gestation.

The mare exhibits nocturnal uterine contractions in the last 6 days of gestation. It is hypothesized that estradiol 17beta (O17beta) may be associated with the nightly increase in uterine contractions. The 24-h secretion pattern of plasma O17beta was measured in 3 pony mares in late gestation to identify changes in release as the mare neared parturition. Blood was collected weekly at 08:00 hours beginning on day 240 and every third day from day 330 until delivery. Serial blood samples were collected from each mare every 30-min for 24-h beginning on gestation day 310 and every sixth day thereafter until parturition. Concentrations of O17beta were elevated at night with lowest concentrations occurring directly before sunset (p < 0.01). The natural log of the variance was increased at sunset (p < 0.01) and was decreased during the 6-h period immediately after sunrise. This pattern was especially evident in the 6 days that preceded parturition. The contrast between nocturnal and daytime concentrations of O17beta in the last 6 days of gestation may contribute to night-time delivery in the mare.

Animals↗
PubMed2001

An integrated visualization system for surgical planning and guidance using image fusion and an open MR.

A surgical guidance and visualization system is presented, which uniquely integrates capabilities for data analysis and on-line interventional guidance into the setting of interventional MRI. Various pre-operative scans (T1- and T2-weighted MRI, MR angiography, and functional MRI (fMRI)) are fused and automatically aligned with the operating field of the interventional MR system. Both pre-surgical and intra-operative data may be segmented to generate three-dimensional surface models of key anatomical and functional structures. Models are combined in a three-dimensional scene along with reformatted slices that are driven by a tracked surgical device. Thus, pre-operative data augments interventional imaging to expedite tissue characterization and precise localization and targeting. As the surgery progresses, and anatomical changes subsequently reduce the relevance of pre-operative data, interventional data is refreshed for software navigation in true real time. The system has been applied in 45 neurosurgical cases and found to have beneficial utility for planning and guidance. J. Magn. Reson. Imaging 2001;13:967-975.

Adolescent↗
PubMed2000

Differential effect of prostaglandins on gallstone-free and gallstone-containing human gallbladder.

Nonsteroidal antiinflammatory drugs, inhibitors of prostaglandin synthesis, have different effects on gallbladder contractility in normal and diseased human gallbladders in vivo. We investigated this differential effect by comparing the effects of prostaglandins PGE2 and PGF2alpha, the thromboxane A2 mimetic U46619, and PGI2 on in vitro contractility in gallstone-free and gallstone-containing human gallbladders. Isometric tension was measured in gallbladder muscle strips mounted in organ baths. EC50 was calculated for each agonist. The rank order of potency in gallstone-free gallbladders was PGE2 > CCK > U46619 > PGF2alpha and in gallstone-containing gallbladders was U46619 > PGE2 > CCK > PGF2alpha. PGI2 produced contraction of gallstone-free gallbladder and relaxation of gallstone-containing gallbladder in the basal state. Further, PGI2 produced no relaxation in gallstone-free muscle strips precontracted with CCK, but significant relaxation in CCK precontracted gallstone-containing strips. PGE2, PGF2alpha, and U46619 are potent contractors of gallstone-free and gallstone-containing gallbladders, whereas PGI2 relaxes only gallstone-containing gallbladders. Since gallbladders containing cholesterol-supersaturated bile produce increased PGI2, this PGI2-induced relaxation may be a determinant of the impaired gallbladder motility of gallstone disease.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

The differential effect of VIP and PACAP on guinea pig gallbladder in vitro.

OBJECTIVES: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a recently identified member of the secretin/glucagon/vasoactive intestinal peptide (VIP) family. Like VIP, PACAP is largely inhibitory in the gastrointestinal tract. The aim of our work was to characterize the effects of PACAP on both contraction and relaxation of guinea pig gallbladder (GPGB) muscle. METHODS: Gallbladder muscle strips were obtained from male Dunkin-Hartley guinea pigs (250-350 g). Isometric tension was measured in strips suspended in gassed (95% O2, 5% CO2) Krebs' solution at 37 degrees C and equilibrated for 60 min. Cumulative additions of VIP or PACAP (10(-9)-10(-6) mol/l) were performed with strips at basal tone or with strips pre-contracted with cholecystokinin-octapeptide (CCK-8). RESULTS: VIP had no effect on basal tone, in contrast with PACAP which produced concentration-dependent contraction to a maximum of 57.9 +/- 24.3% of control (CCK 3 x 10(-7) mol/l). The highest concentration (10(-6) mol/l) of VIP produced a 32 +/- 6% relaxation of 3 x 10(-9) mol/l CCK-8-contracted GPGB. With 3 x 10(-8) mol/l CCK-contracted GPGB strips, VIP produced a 26.7 +/- 6.6% relaxation. PACAP produced a further concentration-dependent contraction of 3 x 10(-9) mol/l CCK-contracted strips which reached 17.5 +/- 9.9% at the maximal concentration used (10(-6) mol/l). PACAP produced a concentration-dependent relaxation of 3 x 10(-8) mol/l CCK-contracted strips which reached a maximum relaxation of 19 +/- 5% of the control. CONCLUSIONS: PACAP has a dual effect on guinea pig gallbladder motility in vitro, producing contraction in the basal state, and both contraction and relaxation in the CCK-contracted state. This is in contrast to the effects of VIP, a closely related peptide.

Animals↗
PubMed1996

L-Arginine, nitric oxide, and intestinal secretion: studies in rat jejunum in vivo.

BACKGROUND: L-Arginine has been shown to induce fluid secretion in human jejunum. Nitric oxide, a derivative of L-arginine is thought to have an important role as an intestinal secretagogue. AIM: To determine the effect of L-arginine and the nitric oxide synthase inhibitor, nitro L-arginine methyl ester (L-NAME), on fluid and electrolyte movement in rat jejunum. METHODS: A 25 cm segment of rat jejunum was perfused in situ with iso-osmotic solutions containing either (1) saline, (2) D-arginine 20, (3) L-arginine 20, (4) L-NAME 0.1, 1, or 20 mmol/l, or (5) a combination of L-arginine 20 and L-NAME 0.1, 1, or 20 mmol/l. In further groups the effect of a subcutaneous injection of L-NAME 100 mg/kg was examined in rats pretreated with either D-or L-arginine 500 mg/kg. RESULTS: L-Arginine, unlike D-arginine, induced fluid secretion despite being better absorbed (mean -7.3 v 17.0 microliters/min/g; p < 0.01). L-NAME at 0.1 mmol/l had no effect on basal fluid movement but reversed L-arginine induced secretion (7.8; p < 0.05). L-NAME at 1 and 20 mmol/l induced fluid secretion (-15.4 and -28.4, respectively), which was enhanced by the addition of L-arginine (-30.0 and -41.0, respectively; both p < 0.05). A subcutaneous injection of L-NAME resulted in marked fluid secretion (-39.9) and histological evidence of intestinal ischaemia. These changes were attenuated or reversed by pretreatment with subcutaneous L- but not D-arginine. CONCLUSIONS: L-arginine induces intestinal fluid secretion through production of nitric oxide. There is a delicate balance between the effect of nitric oxide as a secretagogue and its effect on maintaining blood flow and thus preventing intestinal ischaemia.

Animals↗
PubMed1995

Contractile activity of endothelin precursors in the isolated gallbladder of the guinea-pig: presence of an endothelin-converting enzyme.

A single addition of 3 x I0-7 M ET-1, ET-2 or ET-3 produced contractions that reached a steady state in 28.2 +/- 4.2, 21.1 +/- 1.3 and 24.0 +/- 3.8 min, respectively and took 2.7 +/- 0.4, 2.1 + 0.1 and 1.6 +/- 0.1 min to reach half of this steady-state response.4. Contractions induced by 3 x I0-7 M big ET-11-38 or big ET-11- 39 reached a plateau in 38.5 +/- 3.6 and 35.6 +/- 3.3 min, respectively, and half of these responses were attained in 12.0 +/- 2.5 and 7.1 +/- 1.1 min.Thus, these contractions developed more slowly than those induced by ET-1. Contractions induced by 3 x 10-7 M big ET-21-38 were also much slower to develop than those to ET-2, for these took 49 +/- 2 min to reach plateau and 19.4 +/- 2.1 min to attain half that response. Contractions induced by 3 x 10-7 M big ET-31-41 amide took 50.2 +/- 3.7 min to reach a plateau and 27.3 +/- 3.0 min to reach half of this response.5. Phosphoramidon (0.1, 1 and 3 x 10-4 M) inhibited contractions induced by big ET-11.39. For instance,the contractions induced by 3 x 10-7 M big ET-11-39 were inhibited by 10-4 M or 3 x 10-4 M of phosphoramidon by 62.8 +/- 6.7% or 74.5 +/- 4.6%, respectively. Similarly, contractions induced by ET-21-38 were inhibited by 91.3 +/- 5.4% and the small response induced by big ET-3l-4l amide was abolished by 3 x 10-4M phosphoramidon. Conversely, the neutral endopeptidase (EC 24.11) inhibitor DL-thiorphan(3 x 10-4 M) had no effect. Captopril (10-5 M), pepstatin A (10-5 M), phenylmethylsulphonylfluoride(PMSF, 10-3 M), aprotinin (10-5 M), E-64 (10-5 M), cystatin (10-6 M), leupeptin (10-4 M),chymostatin (10-4 M), or bestatin (10-5 M) did not inhibit but rather increased to a similar, but small degree the contractions induced by 3 to 30 x 10-9 M big ET-11-39. Only captopril (10-5 M) or leupeptin(10-4 M) increased the contraction induced by 3 x 10-7 M big ET-11-39. Phosphoramidon (10-4 M),pepstatin (10-5 M) or PMSF (10-3 M) did not affect contractions induced by ET-1.6. Removal of the epithelium increased by 70% the size of the contraction induced by 5 microM histamine(1.08 +/- 0.05 g; n = 160 to 1.84 +/- 0.14 g; n = 12) but did not affect, in absolute terms, the contraction induced by ET-1 (as a % of the response to histamine, these responses were, of course, apparently depressed). Epithelium removal did, however, increase the size of the contractions induced by 3 to 30 x 10-9 M big ET-1 -39 which was very similar to the effect of the protease inhibitors.7. In competition binding studies on membranes prepared from the guinea-pig gallbladder, 10-11 MET-1 inhibited by 76.9 +/- 3.1% the binding of [125]-ET-I while porcine big ET-11-39 caused no inhibition(0.7 +/- 3.0; n = 3). ET-1 (10-6 M) inhibited binding by 95.7 =/- 1.1% (n = 3) while at this much higher concentration, big ET-11-39 inhibited binding by only 16.8 +/- 4.2% (n = 3). This clearly suggests that big ET-11-39 does not bind directly to ET receptors.8. Thus, a phosphoramidon-sensitive endothelin-converting enzyme (ECE), different from neutral endopeptidase (NEP; EC 24.11) and not located on the epithelium, converts big ET-1 into ET-1 in the gallbladder of the guinea-pig. This ECE appears to act preferentially on big ET-1 or big ET-2 over bigET-3.

Animals↗
PubMed1995

Role of 5-hydroxytryptamine in intestinal water and electrolyte movement during gut anaphylaxis.

Exposure of sensitised intestine to specific allergen is known to produce appreciable reduction in water and electrolyte absorption. The mediators participating in this process have not been fully characterised. The effects of the 5-hydroxytryptamine2 (5-HT2) and 5-HT3 receptor antagonists, ketanserin and granisetron, respectively, on water movement during intestinal anaphylaxis were studied. Hooded Lister rats (120-150 g) were sensitised to ovalbumen and 14 days later, intestinal water and electrolyte movement was assessed at 10 minute intervals by in situ jejunal perfusion with a plasma electrolyte solution (PES) or PES containing 20 mg/l ovalbumen. Within 20 minutes of exposure to PES+ovalbumen, net water secretion that could be completely prevented by the mast cell stabilising agent doxantrazole occurred compared with absorption with PES alone (median -20 microliters/min/g (interquartile range -43 to -5), n = 11), v (107 (86 to 113), n = 10; p < 0.01). Pre-treatment with subcutaneous ketanserin 200 micrograms/kg (n = 7) or granisetron 300 micrograms/kg (n = 8) partially inhibited the secretory response to PES+ovalbumen (18 (11 to 48) and 13 (6 to 32) respectively; both p < 0.01 compared with PES+ovalbumen control). After 40 minutes perfusion with PES+ovalbumen, the changes in water movement were less pronounced 24 (-3 to 43) and neither ketanserin or granisetron had any effect (ketanserin: 48 (28 to 87), granisetron: 41 (32 to 83); NS). In all experiments, sodium and chloride movement paralleled that of water. Thus, the profound water secretion that occurs in the early stages of intestinal anaphylaxis is partly 5-HT dependent because it can be reversed by 5-HT2 and 5-HT3 receptor antagonists. Other mediators must also be involved, especially in the late phase of anaphylaxis.

Anaphylaxis↗
PubMed1995

Role of 5-hydroxytryptamine type 3 receptors in rat intestinal fluid and electrolyte secretion induced by cholera and Escherichia coli enterotoxins.

Cholera toxin and Escherichia coli heat labile toxin (LT) induced intestinal secretion has in the past been attributed exclusively to an increase in intracellular cAMP whereas E coli heat stable toxin (ST) induced secretion is mediated through cGMP. Evidence is accumulating on the importance of 5-hydroxytryptamine (5-HT) in cholera toxin induced secretion, but its role in LT and ST is not well established. This study therefore investigated in vivo the effect of 5-HT3 receptor antagonist, granisetron, on intestinal fluid and electrolyte secretion induced by cholera toxin, LT, and ST. Granisetron (30, 75, 150, or 300 micrograms/kg) was given subcutaneously to adult male Wistar rats 90 minutes before instillation of 75 micrograms cholera toxin or 50 micrograms LT in isolated whole small intestine. In situ small intestinal perfusion was performed with an iso-osmotic plasma electrolyte solution (PES) to assess fluid movement. In a second group of animals, granisetron (300 micrograms/kg) was given subcutaneously and two hours later small intestinal perfusion with PES containing 200 micrograms/l ST was performed. Cholera toxin induced net fluid secretion (median -50.1 microliters/min/g (interquartile range -59.5 to -29.8)) was found to be dose dependently decreased or abolished by granisetron (plateau effect at 75 micrograms/kg: 18 (-7.8 to 28), p < 0.01). Granisetron in high dose (300 micrograms/kg), however, failed to prevent LT or ST induced secretion (-52 (-121 to -71) v -31 (-44 to -18), and (-39 (-49 to 17) v (-22 (-39 to -3)), respectively). Sodium and chloride movement paralleled that of fluid. In conclusion, these data show that 5-HT and 5-HT3 receptors play an important part in cholera toxin induced secretion but are not involved in E coli heat stable or heat labile toxin induced secretion.

Animals↗
PubMed1994

An office guide to whole-gut transit time. Patients' recollection of their stool form.

Forty-seven patients (ages 17-74 years, 33 women) who had irritable bowel syndrome and who attended a gastroenterology clinic had their whole-gut transit time (WGTT) assessed by an abdominal radiograph after ingesting 20 radioopaque markers on 4 consecutive days. Immediately afterward, the patients completed a questionnaire that asked about their stool form on the Bristol Scale, their bowel frequency, and whether they thought they had been experiencing diarrhea or constipation during the previous 5 days. WGTT varied from 7 to 96 h. Stool form correlated significantly with WGTT (r = -0.57, p < 0.001), whereas stool frequency did not (r = 0.31, NS). The regression equation relating WGTT to stool form was WGTT (h) = 75-10 (stool form). WGTT, stool form, and frequency were significantly different in patients reporting constipation compared with those who reported diarrhea, diarrhea and constipation, or neither, but in the last three groups these parameters were not significantly different from each other. Patients' recollection of stool form is a reasonable guide to their transit time and can be used in the office to identify pseudodiarrhea and true constipation.

Adult↗
PubMed1994

Inhibition of 5-hydroxytryptamine re-uptake impairs human gall-bladder emptying.

BACKGROUND: 5-Hydroxytryptamine (5-HT) is an important neurotransmitter in the enteric nervous system. The intrinsic neural plexus of the gall-bladder resembles the enteric nervous system and similarly contains 5-HT neurones. The action of 5-HT on gallbladder motility has been investigated in animals but its effect on the human gall-bladder in vivo is unknown. METHODS: The effect of indirect 5-HT agonism using paroxetine, a specific inhibitor of neuronal 5-HT reuptake, on gall-bladder motility was investigated in 12 healthy volunteers. In a randomized double-blind crossover design, gall-bladder motility was assessed after administration of 30 mg paroxetine daily for two days and after placebo. Ultrasonography was used to determine gall-bladder volumes while fasting and at 5 min intervals following a 250 kcal mixed liquid meal. RESULTS: Fasting gall-bladder volumes of 21.8 +/- 3.2 ml on placebo and 28.0 +/- 3.5 ml on paroxetine were similar. Paroxetine impaired postprandial gall-bladder emptying. Residual gall-bladder volume was 10.2 +/- 2.7 ml with placebo and 17.1 +/- 2.7 ml with paroxetine (P < 0.05). Ejection fraction was 57.3 +/- 7.7% on placebo and 40.9 +/- 4.7% on paroxetine (P < 0.05). CONCLUSION: 5-HT pathways may participate in the regulation of biliary motility, and this study demonstrates an inhibitory role of 5-HT in the control of human gall-bladder emptying.

Adult↗
PubMed1994

Characterization of endothelin (ET) receptors in the isolated gall bladder of the guinea-pig: evidence for an additional ET receptor subtype.

1. We have characterized the receptors mediating contractions induced by endothelin-1 (ET-1), ET-2, ET-3 and the ETB-selective receptor agonists, sarafotoxin 6c (SX6c), IRL 1620, BQ-3020, [Ala1,3,11,15]ET-1 and ET (16-21) in strips of the isolated gall bladder of the guinea-pig (GPGB). We used as antagonists BQ-123 (ETA receptor selective) and PD 145065 (ETA/ETB receptor non-selective). 2. ET-1, ET-2 and ET-3 (10(-10) M to 3 x 10(-7) M) caused similar slowly-developing concentration-dependent contractions of the GPGB. Contractile effects induced by ET-1, ET-2 or ET-3 (at 3 x 10(-7) M) were also similar (230 +/- 25, 241 +/- 7 and 287 +/- 37% of that to histamine at 5 x 10(-6) M, n = 7, 6, 12, respectively). However, the threshold concentration for ET-1 or ET-2 was 10(-10) M whereas it was 3 x 10(-9) M for ET-3. 3. SX6c (10(-10) M to 3 x 10(-7) M) also caused slowly-developing concentration-dependent contractions at a threshold concentration of 10(-10) M (n = 16). However, the contraction caused by SX6c at 3 x 10(-7) M was 116 +/- 9% of that to histamine at 5 x 10(-6) M, which was half of that induced by the same concentration of the ET isopeptides. The contraction induced by IRL 1620 at 3 x 10-7 M (n = 9) was 43 +/- 9% of that to histamine at 5 x 10-6 M, which was one fifth of that produced by the same concentration of ET-1. Contractions induced by BQ-3020 or [Ala1,3,11,15]ET-I at 3 x 10-7 M were even less than those produced by IRL 1620. ET (16-21) was inactive up to 10-5 M. Addition of a concentration of 3 x 10-7 M of ET-1 to tissues with developed contractions induced by the bolus addition of 3 x 10-7 M SX6c caused a further contraction of the GPGB to the level observed with ET-1 alone at 3 x 10-7M (n = 8).4. BQ-123 (10-5 M) did not affect the concentration-response curve to ET-1 and the contraction induced by 3 x 10- M was also not affected (n = 5; 239 +/- 19% of histamine at 5 x 10-6 M). PD 145065(10-5 M) shifted the ET-1 concentration-response curve to the right and the contraction induced by ET-1at 3 x 10-7 M was inhibited by 15% (n = 6; NS). A higher concentration of BQ-123 (10-4 M) caused a significant shift to the right of the ET-1 concentration-response curve similar to that caused by PD 145065 (10-s M) and caused a 24% (n = 6; NS) inhibition of the contractions induced by ET-1 at 3 x 10-7 M. PD 145065 (10-4 M) abolished contractions induced by ET-1 (up to 10- M) and inhibited the response to ET-1 at 3 x 10-7 M by 52% (n = 4; P< 0.05).5. Contractions induced by ET-3 were more sensitive to inhibition by the antagonists. BQ-123 (10-6,10-5 or 10-4 M) inhibited responses to 3 x 10-7 M ET-3 by 66, 71 and 83%, respectively (n = 5, 5, 3;P< 0.05). PD 145065 (10-6, 10-5 or 10-4 M) attenuated more strongly than did BQ-123 the contractions induced by ET-3. For instance, the contractions caused by ET-3 at 3 x 10-7 M were decreased by 73 and 80% (n = 5, 5; P<0.05) in the presence of PD 145065 (10-6 or 10-5 M, respectively). PD 145065(10-4 M) completely abolished contractions to ET-3 (n = 4; up to 3 x 10-7M).6. Contractions induced by SX6c, especially those observed at concentrations lower than 10-8 M, were attenuated by BQ-123 (up to 10-4 M). PD 145065 (10-5M) shifted to the right the concentration response curve to SX6c and inhibited by 38% (P<0.05) the contractions induced by 3 x 10-7M.However, the contractions induced by a bolus addition of a high concentration of SX6c (3 x 10-7 M)and the subsequent addition of an identical concentration of ET-1 on top of SX6c were not affected byBQ-123 (10-6 or 10-5 M).7. These results suggest that ETB receptors are involved in the contractions induced by endothelins in the GPGB. However, SX6c and other selective ETB agonists produced only half or less than half of the contractile response induced by non-selective agonists. In addition, the responses to ET-1 but not to ET-3, were insensitive to the antagonist action of BQ-123 at 10-5 M whereas BQ-123 or PD 145065 at 10-5 M strongly antagonized contractions induced by ET-3. Finally, BQ-123 at 10-4 M inhibited contractions to ET-1 and SX6c. Thus, within the GPGB there may well be additional ET receptor(s) not conforming to the established ETA/ETB receptor subtype classification, as well as ETB receptors.

Amino Acid Sequence↗
PubMed1993

Promotion of gallbladder emptying by intravenous aminoacids.

Patients receiving total intravenous nutrition have inert gallbladders; gallbladder sludge and gallstones often develop, but are preventable if gallbladder emptying can be improved. We measured the effect of giving rapid intravenous infusions of aminoacid solutions in eight normal subjects. Four regimens were tested (250 mL over 30 min, 250 mL over 10 min, 125 mL over 5 min, and 50 mL over 5 min). Gallbladder emptying, as measured by ultrasound and cholecystokinin release, depended on both the amount and the rate of aminoacid infusion. Rapid infusion of 125 mL of an aminoacid mixture (Synthamin 14 without electrolytes) over 5 min (2.1 g per min) produced a 64% reduction in gallbladder volume within 30 min, whereas a 50 mL infusion over 5 min produced only a 22% reduction. Intermittent rapid infusion of small amounts of aminoacids may prevent gallstones in patients receiving intravenous nutrition.

Adult↗
PubMed1993

The roles of enteric bacterial sialidase, sialate O-acetyl esterase and glycosulfatase in the degradation of human colonic mucin.

Sialidase activity in normal faecal extracts showed a preference for mucin-related glycoprotein and oligosaccharide substrates, but the presence of two or more O-acetyl esters at positions C7-C9 on the sialic acids retarded the rate of hydrolysis. A specific sialate O-acetyl esterase was detected with a lower total activity relative to sialidase with mucin substrates and having a pH optimum of 7.8 and a KM of approximately 1 mM sialate O-acetyl ester. A specific glycosulfatase activity was found in faecal extracts using the substrate lactit-[3H]ol 6-O-sulfate with a pH optimum of pH 5.0 and a KM of approximately 1 mM. Faecal extracts from ulcerative colitis (UC) patients had higher sialate O-acetyl esterase and glycosulfatase activity, while mucin sialidase activity was unchanged. Metabolically labelled mucin isolated from UC patients contained less sulfate and had lower sialic acid O-acetylation compared with normal mucin. Colonic mucin was degraded more efficiently by faecal extracts from UC patients compared with normal extracts. The UC mucin was degraded more rapidly than the normal mucin by faecal enzyme extracts from both normal and UC subjects.

Acetylation↗