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Biomedical subjects

M Gregor

Publications and source records attributed to M Gregor.

At least 127 records · Page 7Linked to original sources

Lack of adaptive changes in human pancreatic amylase and lipase secretion in response to high-carbohydrate, low-fat diet applied by a 10-day continuous intraduodenal infusion.

In order to investigate whether the human exocrine pancreas is capable of adapting to a diet with a high-carbohydrate, low-fat, and normal protein content, 10 healthy subjects were given a continuous intraduodenal infusion of such a dietary composition (8760 kJ in 2400 ml/day) via a portable infusion pump over a period of 10 days. The diet consisted of 76% of calories as carbohydrates (80% oligosaccharides, 20% mono- and disaccharides), 10% as fat (more than 90% C18 fatty acids) and 14% as protein (oligo- and polypeptides; 11.8 g nitrogen per day). A complete pancreozymin-secretin test was carried out before and after the experimental period. The results show that the above dietary regimen leads to a significant (P less than 0.05) increase in the stimulated secretion rates of trypsin and chymotrypsin, whereas, in contrast to the findings in animal experiments, no change could be measured in the secretion rates of amylase and lipase.

Adaptation, Physiological↗

Production and characterization of N-terminally and C-terminally directed monoclonal antibodies against pancreatic glucagon.

Hybridoma technology has been successfully applied to the production of monoclonal antibodies against a variety of small soluble peptides. We report herein for the first time on the development of monoclonal antibodies to pancreatic glucagon. Twenty-three stable positive hybridomas were detected by radioimmunoassay from five separate fusions and cloned by the limiting dilution method. Four selected monoclonal antibodies were all of the IgG 2a subclass type kappa and bound to protein A. One monoclonal antibody (23.8B6) was shown to be directed toward the C-terminal region and another (23.6B4) toward the N-terminal to central region of the glucagon molecule. These antibodies did not cross-react with any of the other peptides tested. Two further monoclonal antibodies (23.4A1, 22.3A6) reacted with the C-terminal third of the glucagon molecule and showed a cross-reaction with the structurally related gastric inhibitory polypeptide of 0.7% and 9.1%, respectively. All but the C-terminal monoclonal antibody 23.8B6 showed a marked cross-reaction with ileal extracts. The N-terminally directed monoclonal antibody 23.6B4 was of sufficient avidity for use in the radioimmunoassay of pancreatic glucagon and gut glucagon-like immunoreactivity in tissue extracts, being sensitive to changes of pancreatic glucagon of 2.0 fmol/tube at a final titer of culture supernatant of 1:1.4 X 10(5). In gel permeation chromatography of intestinal extracts, two major peaks were detectable (Kav 0.27 and 0.54). The present findings show that monoclonal antibodies provide sensitive tools for detecting pancreatic glucagon and gut glucagon-like immunoreactivity. They will be valuable immunoreactants for the development of immunoradiometric assays as well as for large-scale immunoaffinity purification of gut glucagon-like immunoreactivity.

Animals↗

Glucagon and small-bowel mucosa.

Numerous functional and structural effects of pharmacological dosages of glucagon on the small-intestinal mucosa have been demonstrated. In addition, clinical conditions associated with elevated concentrations of plasma glucagon may go along with alterations of the intestinal mucosa. The physiological and pathophysiological relevance of these findings, however, is questionable in view of the heterogeneity of the findings, of the complexity of the experimental systems used and of the methodological problems involved. With respect to possible trophic effects on the small-bowel mucosa enteroglucagon is of special importance. Numerous diseases in which increased intestinal mucosal growth has been shown are associated with elevated plasma concentrations of enteroglucagon. Our results concerning radiation damage, the time course of plasma enteroglucagon levels during antimitotic treatment, the small intestinal resection and the experimental blind loop syndrome are discussed. An outlook will be given as to the use of monoclonal antibodies in the development of glucagon as well as enteroglucagon deficiency states for the study of the physiological relevance of these two regulatory peptides.

Adaptation, Physiological↗

[Simplified procedure for endoscopic administration of enteral feeding catheters].

Due to the immobilisation of patients in intensive care units or to pathologic alterations in the upper gastrointestinal tract caused by stenosis or anastomosis, the insertion of feeding tubes into the duodenum has been difficult in some cases. For this reason an enteral feeding tube has been developed which can be introduced through the biopsy channel of an endoscope so that it is possible to place the tube under visual control. This method has been used in more than 20 patients; in each case the positioning of the tube and the consecutive nutrition were free of complications. The required material is now commercially available.

Critical Care↗

Pancreatic glucagon in human foetal stomach.

A combination of immunocytochemistry at light and electron microscopic levels, direct radioimmunoassay and measurement after gel chromatography have been used to identify and characterise a glucagon-like peptide detected in human foetal stomach. Immunocytochemistry, with region specific antisera, demonstrated that the glucagon-containing cells were indistinguishable from pancreatic A cells. Radioimmunoassay of tissue extracts confirmed the presence of significant quantities of glucagon, mean 21 pmol/g wet weight (range 14-29) in 16-26 week old foetuses, increasing to 41 pmol/g wet weight (range 31-52) in 33-30 week old foetuses and after gel chromatography the peptide was found to elute at the same position as standard porcine glucagon. It is apparent, therefore, that the human foetal fundus contains significant quantities of true pancreatic-type glucagon.

Female↗

Pattern of plasma cortisol during the 24-hour sleep/wake cycle in the rhesus monkey.

The 24-h pattern of plasma cortisol and changes induced by alterations of the sleep/wake cycle were studied in 12 male rhesus monkeys. The chair-living animals were chronically prepared with a right atrial catheter and electroencephalogram electrodes. Hormone (blood samples every 15 min) and continuous activity/electroencephalogram profiles were obtained from the adjacent room for 96 h (4 animals), 24 h or various shorter periods of time. Plasma cortisol showed a circadian rhythm with a late evening minimum (1900-2100 h; approximately 60 micrograms/liter) and an early morning maximum (0400-0700 h; approximately 160 micrograms/liter). Superimposed were episodic fluctuations for which powerspectral analysis showed a weakly expressed 30- to 60-min periodicity in 24 of 27 24-h profiles. Cross-correlation analysis indicated no relation between cortisol on the one hand and daytime activity-arousal, nocturnal waking, slow wave sleep (SWS) or rapid eye movement sleep (REM), respectively. Five-hour total sleep deprivation, specific SWS-deprivation, and severe disruption of the REM-pattern provided no evidence for an immediate effect of sleep onset or sleep stages on the cortisol pattern. Cortisol rose significantly after termination of the 5-h deprivation, but the mechanism of this elevation remains to be determined. Cross-correlation analysis between the cortisol time series and those of GH, PRL, and TSH from already published data gave no evidence for a regular temporal relationship between the episodic patterns of these hormones.

Animals↗

Development of intestinal regulatory peptides in the human fetus.

The time of first appearance and subsequent development of eight regulatory peptides in the small and large intestine of human fetuses has been investigated. Gastrin, secretin, motilin, gastric inhibitory peptide, vasoactive intestinal peptide, enteroglucagon, and somatostatin were first detected as early as 8 wk of age, while neurotensin was only demonstrated at 12 wk. Adult patterns of distribution were established by 20 wk of age. Of the peptides examined only vasoactive intestinal peptide was localized to nerve fibers and these were seen clearly in the myenteric plexus at the 12-wk fetal stage and in the later fetuses in both the enteric plexuses. The concentrations of regulatory peptides increased steadily until term when they were close to adult levels. Secretin and vasoactive intestinal peptide showed only a single molecular size species by gel permeation chromatography but the other peptides showed multiple peaks, the ratios tending to change through the gestational period in favor of the smaller molecular sized moieties. Thus the regulatory peptide system of the gut is present in th early fetus and its role in the process of maturation requires investigation.

Chromatography, Gel↗

Twenty-four-hour pattern of growth hormone secretion in the rhesus monkey: studies including alterations of the sleep/wake and sleep stage cycles.

The 24-h pattern of GH secretion and its possible relation to the sleep/wake cycle and to sleep stages were studied in 12 male rhesus monkeys. Blood samples were drawn every 15 min for 96 h, 24 h, or shorter periods of time through chronic right atrial catheters which extended through the wall into the adjacent room. In addition, activity rating (daytime) and determination of sleep stages from electroencephalogram recordings (nighttime) were done. GH profiles were obtained during undisturbed conditions and during deprivation of nap, 5 h total sleep, slow wave sleep (SWS), and rapid eye movement (REM) sleep. GH secretion was episodic, with peak concentrations often exceeding 20 ngeq/ml and nadirs mostly below 1 ngeq/ml. Autocorrelation analysis demonstrated a circadian and an ultradian rhythm during undisturbed conditions. However, the cycle length of the ultradian rhythm showed large inter- and intraindividual variations (from 3--6 h). Neither cross-correlation analysis between hormonal and activity/electroencephalogram sleep stage time series nor results of deprivation experiments produced evidence for a link between nap phases, the sleep/wake cycle, or the SWS/REM sleep stage cycle on the one hand and the GH secretory pattern on the other hand. However, while SWS deprivation was highly effective, REM deprivation did not substantially reduce total REM sleep time due to frequent entries into abortive REM sleep epochs. During the daytime, there was no significant correlation between activity/arousal and GH, but during the night, there was a significant positive correlation between stage waking and GH. A direct or indirect synchronizing effect of the matutinal light change is suggested by the pattern of the 24-h curve of mean GH concentrations during undisturbed conditions: a steep increase from very low concentrations at light onset, followed by a succession of nadirs and peaks at approximately 4.5-h intervals. However, the nadirs became progressively more shallow until there was no apparent periodicity during the night due to the loss of synchronization. It is concluded that GH in the rhesus monkey shows a circadian and an ultradian periodicity. However, in contrast to man, sleep and SWS are not important determinators of the 24-h GH pattern.

Animals↗

[The use of determining the sound intensity of diagnostic ultrasonic equipment in obstetrics (author's transl)].

The possible risks when using help energy ultrasound have resulted in worldwide "standard committees" establishing guiding values for the sound intensity which must not be exceeded by diagnostic equipment, 100 mW/cm2 are commonly accepted. The intensity level can be measured with a special very small microphone. The highest values occur at distances of near field length (also "standard working distance") or in the focal point. For measurements of sound intensities of different equipment (Real-time-scanner, Compound-scanner, Encephalographs, Doppler-unit) we used a sonic microphone which was calibrated by the "Physikalische Technische Bundesanstalt" (Physical-Technical Federal Institute). The measurements were carried out in water and correspond approximately to the value in human tissue. Using focusing transducers the sound intensity was much higher than without focusing transducers. Working with such a modern transducer and an old compound-scanner the measurement gave approximately 300 milliwatt per square centimeter. The results show that focusing trasducers cannot be used without a great deal of forethought.

Female↗

Gut hormones in tropical malabsorption.

Concentrations of various gut hormones were measured after a test breakfast in eight patients with severe tropical malabsorption and 12 controls. The patients with tropical malabsorption had greatly raised basal plasma motilin and enteroglucagon concentrations, but their postprandial release of both gastric inhibitory polypeptide and insulin was significantly reduced. The pattern of gut hormone release differed from that found in coeliac disease. The measurement of gut hormones, each of which has a specific site and function, thus throws new light on the pathophysiology of tropical malabsorption and may suggest approaches of treatment.

Adult↗

Cardiac and respiratory rhythmicities in cutaneous and muscle vasoconstrictor neurones to the cat's hindlimb.

Cardiac and respiratory rhythmicities have been investigated quantitatively in postganglionic vasoconstrictor neurones supplying skeletal muscle and skin of the hindlimb in chloralose anesthetized, immobilized cats. Both rhythmicities are largest in muscle vasoconstrictor neurones, smaller in vasoconstrictor neurones supplying hariy skin, and smallest in vasoconstrictor neurones supplying hairless skin. The magnitude of the cardiac rhythmicity in the vasoconstrictor neurones is positively correlated with the quantitative reaction to systemic hypoxia.

Animals↗

Effects of sytemic hypoxia and hypercapnia on cutaneous and muscle vasoconstrictor neurones to the cat's hindlimb.

1. Reactions of cutaneous and muscle vasoconstrictor neurones to the hindlimb on systemic hypoxia and systemic hypercapnia were investigated in chloralose anaesthetized cats. Mainly four types of preparations were used: brain intact and decrebrate (pontomedullary) animals with and without carotid sinus (CSN) and vagal nerves (VN). 2. In brain intact animals with intact CSN and VN most cutaneous vasoconstrictor neurones were depressed and most muscle vasoconstrictor neurones were excited during systemic hypoxia and hypercapnia. The responses to hypercapnia were smaller than those to hypoxia. 3. In brain intact deafferented animals and in decerebrate animals with and without intact CSN and VN systemic hypoxia and hypercapnia induced excitation in both cutaneous and muscle vasoconstrictor neurones. The responses to hypoxia were significantly smaller in deafferented preparations when compared to those in preparations with intact CSN and VN. Furthermore in muscle vasoconstrictor neurones the size of the responses was not significantly different in decerebrate preparations from that in brain intact preparations. 4. These results indicate a distinct neuronal organization of the chemoreceptor reflexes in the vasoconstrictor systems in the brain stem. Suprapontine brain structures are most important for producing the inhibition of the cutaneous vasoconstrictor neurones during hypoxia and hypercapnia.

Animals↗

Response pattern of cutaneous postganglionic neurones to the hindlimb on spinal cord heating and cooling in the cat.

Single postganglionic neurones to hairy skin and hairless skin of the hindleg were investigated on spinal cord heating and spinal cord cooling in chloralose anesthetized cats. 1. Spontaneously active postganglionic neurones which were classified as vasoconstrictor neurones were depressed by spinal cord heating and excited by spinal cord cooling. The overall response to spinal cord cooling was smaller than that to spinal cord heating. 2. Postganglionic neurones to the hairless skin, which had most likely sudomotor function, responded initially to spinal cord heating with a few impulses or not at all. As judged by the skin potentials recorded from the hairless skin the sweat glands were also only weakly activated at the beginning of the heat stimuli. 3. Six silent postganglionic neurones, 3 each to the hairy skin and to the hairless skin, were excited during spinal cord heating. The response of these neurones consisted of a dynamic and a static component and started at the beginning of the heating stimuli with latencies of less than 10S. The neurones could not be excited by any other stimuli and were classified as cutaneous vasodilator neurones. 4. Quantitative analysis of 4 spontaneously active postganglionic (vasoconstrictor) neurones and 3 silent postganglionic (vasodilator) neurones revealed that the threshold of the responses of these neurones to spinal cord heating was 40-42 degrees C (on the dorsal spinal cord) and that the response increase was maximal at the highest temperatures tested (43-44 degrees C).¿

Animals↗