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Biomedical subjects

T L Peeters

Publications and source records attributed to T L Peeters.

At least 109 records · Page 6Linked to original sources

The activity front of the migrating motor complex of the human stomach but not of the small intestine is motilin-dependent.

The role of motilin in the generation of the gastric component of phase 3 of the migrating myoelectric complex (MMC) was studied in human volunteers. Interdigestive motor activity was recorded manometrically in five normal subjects after a fast of at least 15 h. Intraluminal pressures were measured in the gastric antrum at 4 levels 3 cm apart and in the upper small bowel at 3 levels 25 cm apart. Blood samples were drawn every 10 min for radioimmunoassay of motilin and PP. After 2 spontaneously occurring activity fronts (AF) had been recorded, bovine PP was infused intravenously at a rate of 50 micrograms/h. Following the third AF a combination of PP (50 micrograms/h) and 13-norleucine-motilin (30 micrograms/h) was infused until after the next AF. It was found that 90% of the spontaneous AFs originated in the stomach. They were preceded by a motilin peak. During the PP infusion, plasma PP levels increased from 29 to 256 pmol/l, motilin decreased from 42 to 15 pmol/l, and all AFs originated in the small bowel. During the combined PP and motilin infusion, plasma motilin increased to 330 pmol/l, and all AFs again originated in the stomach. It is concluded that motilin has an important role in the regulation of the MMC activity front in the stomach, but not in the small intestine. Postprandial rises in plasma PP might be involved in lowering motilin levels after a meal, and indirectly, in the disruption of gastric MMCs during digestion.

Adult↗

Pancreatic polypeptide is not involved in the regulation of the migrating motor complex in man.

The role of pancreatic polypeptide (PP) and motilin in the regulation of the migrating motor complex (MMC) was studied in normal subjects. Both plasma motilin and PP levels changed cyclically in the fasted state and were highest in the late phase II period preceding the activity front in the duodenum. A continental breakfast invariably disrupted the MMC and induced a fed pattern of motility. After the meal plasma motilin levels decreased whereas PP levels rose significantly. Infusion of pure porcine motilin during the fasted state induced an activity front and a rise in plasma PP levels. Infusion of bovine PP in doses producing plasma PP levels above the postprandial values neither induced an activity front nor prevented its occurrence. During PP infusion, however, plasma motilin levels were low, although the activity front was not inhibited. PP seems to have no clear role in the regulation of the motor component of the MMC of man. The role of motilin in the production of the activity front of the MMC is discussed.

Duodenum↗

Simple extraction method and radioimmunoassay for somatostatin in human plasma.

Interference by human plasma proteins in the radioimmunological determination of somatostatin was eliminated by subjecting plasma samples to acid--ethanol precipitation. The assay was performed on the lyophilized supernate from 300 microliters of human plasma, with reagents that are commercially available. Sensitivity was 2.6 pg, corresponding to 8.7 ng/L of plasma. The intra-assay CV was 8%; the inter-assay CV was 12% for a low (30 ng/L) and 15% for a high (100 ng/L) standard. The mean analytical recovery of exogenous somatostatin from plasma was 95%, and the standard synthetic cyclic somatostatin showed parallel dilution curves with extracted plasma samples. Neither gastrin HG-17 and HG-34, pentagastrin, secretin, glucagon, vasoactive intestinal polypeptide, substance P, nor pancreatic polypeptide interfered in the assay system. Mean immunoreactive somatostatin in 20 normal fasting subjects was 31.5 (SD 15.6) ng/L and ranged from 14 to 67 ng/L.

Cross Reactions↗

Bile acid output and the interdigestive migrating motor complex in normals and in cholecystectomy patients.

Bile acid output in the duodenum was studied in relation to the interdigestive migrating motor complex in normal subjects and in cholecystectomy patients. In normal volunteers the bile acid output preceding a duodenal activity front (217 +/- 89 mumol/30 min) was 374% of the output following a front (58 +/- 24 mumol/30 min) (P < 0.05). In cholecystectomy patients the prefront output (354 +/- 64 mumol/30 min) was 195% of the value obtained in the postfront period (234 +/- 59 mumol/30 min) (P < 0.05). These results indicate that the bile acid output into the duodenum during the interdigestive phase in fluctuating in accordance with the interdigestive motility complex.

Bile Acids and Salts↗

Fasting plasma motilin levels are related to the interdigestive motility complex.

Fluctuations of plasma motilin and gastrin levels were analyzed in relation to the interdigestive motor complex in humans, taking the onset of a duodenal activity front (phase 3 of the complex) as a reference point and the time lapse between two fronts as a time base. Statistical analysis showed a close relation between motilin fluctuations and the occurrence of duodenal activity fronts.

Duodenum↗

Motilin and the interdigestive migrating motor complex in man.

In order to assess the possible role of the new candidate gut hormone, motilin, in controlling the interdigestive migrating motor complex (MMC) in man, 14 normal subjects were studied after an overnight fast by means of three pressure-recording catheters with orifices 25 cm apart in the upper small intestine. The typical aboral progressing bursts of pressure waves occurred at a mean interval of 137 minutes and were preceded by a peak motilin level 25 pmol/liter higher than the lowest level in the postactivity-front quiescent period. To study the effect of exogenous motilin, an infusion of pure porcine motilin at various dose levels was given to 16 normal volunteers shortly after the onset of the phase I quiescent period. Motilin infusion induced an activity front in 12 of the 16 subjects. The mean activity front interval was reduced to 46 min (P less than 0.001). This effect could be obtained even at the low dose level of 0.4 pmol/kg/min, which produced an increase in plasma motilin level of only 57 pmol/liter. These data suggest that a cyclic rise in plasma motilin levels is one of the factors involved in the production of the activity front of the migrating motor complex in man.

Adolescent↗

The secretory component of the interdigestive migrating motor complex in man.

Intraduodenal pH, bicarbonate and amylase secretion, and gastric acid and pepsin output were studied in relation to the migrating motor complex in man. The occurrence of a motor complex in the duodenum was preceded by an increase in gastric acid and pepsin output and followed by a peak in bicarbonate and amylase secretion. It is concluded that the interdigestive phase in man is characterized by periodic activity complexes comprising both motor and secretory components. These observations may have important implications for the interpretation of currently used functional tests of gastrointestinal secretion.

Amylases↗

Radioimmunoassay for urinary lysozyme in human serum from leukemic patients.

We present a radioimmunoassay for lysozyme in human serum, based upon human lysozyme isolated from the urine of leukemic patients and antiserum prepared against this lysozyme in the goat. In the separation step, a second antibody is used. By properly adjusting the concentrations of unlabeled and 125I-labeled lysozyme and of the antibodies, maximal precision (SD, 0.04 mg/litre) was obtained in the range 0.00 to 2.00 mg/litre. In 20 normal volunteers the lysozyme concentration was 4.6 +/- 0.8 mg/litre (mean +/- SD), in 13 patients with monocytic leukemia 34.4 +/- 8.6 mg/litre. Correlation with lysoplate determinations was excellent in leukemic sera (r = 0.97) but was poor in normal sera (r = 0.35), possibly owing to the existence of isoenzymes.

Humans↗

Factors influencing lysozyme determinations by the lysoplate method.

Some factors influencing the lysoplate method have been investigated. The influences of pH, ionic strength and temperature of the gel medium can be explained by considering the influence of these factors upon the diffusion rate rather than upon the enzymatic properties of lysozyme. Salts and proteins present in a sample probably affect the results in a similar way. Although the method has a variation coefficient around 10% and thus an acceptable precision, its accuracy is variable and doubtful. The method could be clinically interesting, by discriminating lysozyme isoenzymes, or by indirectly detecting proteins associated with some disease states.

Biological Assay↗

Choice of monitoring isotope in double label radioimmunoassays with nonimmunological separation techniques.

We discuss the suitability of some radioactive isotopes as volume markers in radioimmunoassays, from a radiochemical point of view. For three eligible isotopes (22Na, 60Co, and 75Se) we studied the concentration of the marker in the precipitate formed in the separation phase of radioimmunoassays. For all those kinds of separations tested (charcoal, ammonium sulfate, polyethylene glycol, and ethanol), binding or coprecipitation was virtually absent or negligible with 22Na but 75Se was strongly concentrated in the precipitate. Concentration of 60Co occurred only with charcoal and ethanol precipitation. Because heavy metals tend to bind to serum proteins, we conclude that of all radioactive isotopes commercially available only 22Na should be used in radioimmunoassays with nonimmunological separation methods.

Charcoal↗

Purification and partial characterization of lysozyme from mouse small intestine.

Lysozyme was isolated from the small intestine of mice by combined ion-exchange and molecular sieve chromatography. This lysozyme differs from that isolated from the urine of mice with monocytoma in amino acid composition, and migration rate in cellulose acetate electrophoresis. As intestinal lysozyme originates at least in part from the Paneth cell, our results point towards the existence of isozymes of lysozymes in mice.

Amino Acids↗

Serum lysozyme levels in Crohn's disease and ulcerative colitis.

Serum lysozyme levels were determined in healthy volunteers, patients with Crohn's disease, and patients with ulcerative colitis. The mean concentration in Crohn's disease was significantly greater than in the other groups. In patients with Crohn's disease, as well as in patients with ulcerative colitis, the lysozyme levels correlated with the severity of the disease process and with the extent of the lesions: the more severe the disease and the more extensive the involvement, the higher the lysozyme levels. However, the lysozyme values of the different groups overlapped considerably. Our results indicate that lysozyme determinations have only limited discriminative value for the diagnosis of Crohn's disease and for determining the severity and the extent of the disease process in the individual patient.

Adolescent↗

The erythromycin derivative EM-523 is a potent motilin agonist in man and in rabbit.

Erythromycin may stimulate gastrointestinal motor activity via its effect upon motilin receptors. We have studied the ability of the derivative EM-523 [de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal] to induce contractions in duodenal smooth muscle strips and to displace labeled motilin bound to antral smooth muscle, in man and in rabbit. In both species EM-523 approached the potency of motilin for inducing contractions. Thus pED50 values were 7.84 +/- 0.11 and 8.69 +/- 0.12 for motilin in, respectively, man and rabbit, against 6.08 +/- 0.13 and 8.19 +/- 0.10 for EM-523. In rabbit the efficacy of both compounds decreased in parallel aborally, the responses to EM-523 could not be blocked by atropine (10(-7) M) or TTX (10(-7) M), and both compounds were unable to further enhance the maximum effect to the other compound. In binding studies the order of potency was the same as in the contraction studies. The pIC50 values were: motilin (8.84 +/- 0.31, 9.17 +/- 0.20) greater than EM-523 (7.89 +/- 0.1, 8.40 +/- 0.10). A Schild plot revealed that EM-523 was a competitive inhibitor of motilin receptor binding in man and in rabbit. We conclude that EM-523 is a potent motilin agonist.

Animals↗

Motilin receptors of the rabbit colon.

Binding studies with iodinated motilin revealed that in the small intestine motilin receptor density decreased aborally, disappeared in the caecum but returned in the colon and rectum. The highest density was in the distal colon (112 +/-/11 fmol/mg protein). The dissociation constant was the same in all regions (overall mean 1.10 +/- 0.22 nM). The ability of erythromycin-A (EM-A) and of two derivatives, EM-A N-oxide and EM-523, to displace motilin showed no difference between the tissues studied. Their order of potency was: motilin greater than EM-523 greater than EM-A greater than EM-A N-oxide. Proximal circular colonic smooth muscle strips showed maximal contractile responses towards motilin, EM-523 and EM-A of, respectively, 80 +/- 3%, 78 +/- 4% and 84 +/- 2% relative to the maximum obtained with acetylcholine. In proximal longitudinal muscle only a response of +/- 20% was obtained. Similar responses were obtained in the distal colon. The order of potency to induce contractions as reflected in the pED50 values was: motilin (8.03 +/- 0.1) greater than EM-523 (7.55 +/- 0.03) greater than EM-A (5.84 +/- 0.04) in proximal circular colon. The responses were not blocked by TTX (10(-6) M) or atropine (10(-6) M), but were reduced by verapamil (10(-6)M). The abundance of motilin receptors in colonic smooth muscle, if applicable to other species, opens new perspectives for the therapeutic applications of macrolides with motilin agonist properties.

Acetylcholine↗