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Biomedical subjects

G L Ferri

Publications and source records attributed to G L Ferri.

At least 55 records · Page 3Linked to original sources

Radioimmunoassay and intramural distribution of PHI-IR in human intestine.

The objective of this study was to develop a radioimmunoassay for PHI and use this to assess its intramural distribution in the human intestine. The antibody was harvested following immunization with porcine PHI conjugated to bovine serum albumin by glutaraldehyde, and the iodinated PHI tracer was prepared by the Iodo-gen method. The assay system showed no cross-reaction with other members of the glucagon-secretin family of peptides and was sensitive to changes of PHI of 2 fmol/tube (95% confidence). High concentrations of immunoreactive PHI were found in the human intestine, exclusively localized in the nonendocrine gut layers, suggesting a possible neuroendocrinological or neurotransmitter role for PHI.

Chromatography↗

Immunocytochemical evidence for the presence of gamma 1-MSH-like immunoreactivity in pituitary corticotrophs and ACTH-producing tumours.

The presence of gamma 1-MSH has been demonstrated in bovine neuro-intermediate lobe by biochemical methods, thus suggesting that this peptide is cleaved from the cryptic region of pro-opiocortin. In this study we report the localisation of gamma 1-MSH-like immunoreactivity in the adenohypophysis of man, ox, pig, dog and guinea-pig using immunocytochemical procedures at both light and electron microscope levels. Antisera recognising the C-terminal Arg-Phe-amide and the C-terminal penta-peptide-amide of gamma 1-MSH have been used throughout this study. The immunostaining was found in all endocrine cells of the pars intermedia (where present) and in scattered cells of the pars distalis identified as corticotrophs. No gamma 1-MSH immunoreactivity was detected in rat adenohypophysis. In addition, 7 ACTH-producing tumours (1 pituitary adenoma and 6 ectopic) were investigated and shown to contain gamma 1-MSH immunoreactive cells.

ACTH Syndrome, Ectopic↗

Ileal enteroglucagon cells after ileal-duodenal transposition in the rat.

The changes occurring in the ileal wall and in enteroglucagon cells were studied in a rat model of intestinal adaptation, obtained by the transposition of a segment of distal ileum into the mid-duodenum (6 rats, compared with 6 transected controls). After 40 days, the transposed ileal segment, compared to the equivalent segment in the controls, showed striking increase in weight, especially of the epithelium (1,585 +/- 127 vs. 305 +/- 42 mg, mean +/- SEM, p less than 0.0005). The calculated weight of enteroglucagon cells in the segment showed a smaller, but significant increase (1.7 +/- 0.3 vs. 0.8 +/- 0.2 micrograms, p less than 0.05). Plasma enteroglucagon was markedly raised (239 +/- 28 vs. 61 +/- 7.1 pmol/l, p less than 0.0005) and showed a greatly increased meal-stimulated response (1,521 +/- 284 vs. 83 +/- 43 pmol, p less than 0.0005), thus suggesting hyperactivity of enteroglucagon cells.

Animals↗

Tissue localization and relative distribution of regulatory peptides in separated layers from the human bowel.

The localization and distribution of regulatory peptides was studied in separated epithelium, lamina propria, submucosa, and external muscular layer from 16 specimens of human bowel. Immunoreactive enteroglucagon, gastric inhibitory polypeptide, and neurotensin were almost confined to the epithelial fraction (97.5 +/- 2.2%, 97.5 +/- 4.2%, and 99.3 +/- 1.1% of their respective total content, mean +/- SEM) and were only localized in endocrine cells. Vasoactive intestinal polypeptide-, substance P-, and bombesinlike peptides were virtually restricted to the nonepithelial layers (99.6 +/- 0.2%, 99.6 +/- 0.2%, and 100%) and were demonstrated exclusively in nerves. A particularly rich vasoactive intestinal polypeptide- and substance P-immunoreactive nerve supply was seen in the nonepithelial mucosa, which contained the highest concentrations of these peptides, while bombesin was mainly recovered from the external muscle (87.7 +/- 2.7%). Somatostatin, measured with an antiserum highly specific for somatostatin-14, was found throughout the wall, mainly in the epithelium (39.9 +/- 5.2%) and lamina propria (29.5 +/- 5.9%), but could be immunostained only in endocrine cells.

Aged↗

Mapping, quantitative distribution and origin of substance p- and VIP-containing nerves in the uvea of guinea pig eye.

VIP- and substance P-like immunoreactivities were found in considerable concentrations (VIP: 17.3 +/- 4.8 pmol/g, mean +/- SEM; substance P:11.1 +/- 1.8 pmol/g) in the uveal portion of the guinea pig eye. Immunocytochemistry localised these two regulatory peptides to nerve fibres found principally in a plexus in the iris (substance P) and in an extensive network surrounding the blood vessels of the choroid (VIP). A remarkable anatomical demarcation of the two types of peptide-containing nerves was established by the staining of substance P-containing nerves, which stops at the level of the ciliary body. This uveal area is known to be involved in the ocular responses to nociceptive stimuli. At the ultrastructural level, immunoreactivity for both peptides was localised to distinct subpopulations of p-type nerves, distinguishable by the size of their large dense-cored vesicles. Those immunoreactive for VIP were significantly larger (p less than 0.0005) than those immunoreactive for substance P (95 +/- 7 nm and 82 +/- 9 nm respectively; mean +/- SD). Interruption of the trigeminal pathway produced a remarkable decrease of substance P immunoreactivity in the anterior portion of the uvea (9.1 +/- 1.5 pmol/g, mean +/- SEM, control; 5.3 +/- 1.3 pmol/g, denervated), but not of VIP immunoreactivity in the choroid. Following colchicine treatment, VIP-immunoreactive neuronal cell bodies were localised in the choroid. The separate anatomical localisations and distributions of the two uveal peptides appear to be related to their different origins and functional roles in the response of the eye to noxious stimuli.

Acetylcholinesterase↗

Peptide-containing innervation of the human intestinal mucosa. An immunocytochemical study on whole-mount preparations.

The three-dimensional distribution of the peptide-containing innervation in the human intestinal mucosa was studied by fluorescence immunohistochemistry on whole-mount mucosal preparations. An extensive VIP-immunoreactive nerve supply was demonstrated at all levels, but was markedly increased in density in the distal intestine, where it formed a particularly rich network in close contact with the luminal epithelium. In contrast, substance P-containing nerve fibres formed a looser and evenly distributed innervation at all levels. The muscularis mucosae was richly supplied by VIP- and substance P-containing fibres. Met-enkephalin immunoreactivity was confined to a few scattered nerve bundles running in the muscularis mucosae and around the bottom of epithelial crypts.

Animals↗

Peptidergic nerves.

In recent years the autonomic nervous system has been shown to consist of nerves containing a number of different neurotransmitter substances; a system far more complex than was originally thought. It has been demonstrated that a large part of the autonomic nervous system contains peptides, and that, in the gut, these nerves form a major complex that infiltrates the entire length and breadth of the tract. The detailed study of this peptidergic system has been facilitated by the development of specialised immunocytochemical methods, which have yielded information on the distribution and morphology of the various types of nerve. Thus, the distribution of these nerves can often be seen to parallel what is known about the actions of individual peptides. The majority of peptidergic nerves are intrinsic to the gut, forming, with the other intrinsic nerves, what appears to be a largely autonomous unit. This enteric system can be visualised as a "minibrain", under the general influence of the central nervous system but able to function, to a certain extent, by itself. The consequences of a breakdown in the normal functioning of this system can be seen in a number of gut diseases.

Animals↗

Neuron specific enolase: a common marker for the endocrine cells and innervation of the gut and pancreas.

Neuron specific enolase, the most acidic isoenzyme of the glycolytic enzyme enolase, was first believed to be present exclusively in central neurons. More recently, it has been found in peripheral autonomic nerves and in a number of endocrine cells. An immunocytochemical study was carried out concerning the distribution of neuron specific enolase in the gastrointestinal tract and pancreas of humans and rats. In addition, immunocytochemistry and histochemistry were used to obtain a characterization of the different types of cells and nerves in which neuron specific enolase can be detected. Neuron specific enolase was found in all currently identifiable endocrine cell types and nerves of the gut and pancreas. Neuron specific enolase is therefore a common marker for both endocrine cells and enteric nerves, thus providing a simple means for their simultaneous demonstration and examination of their morphologic characteristics and integration.

Animals↗

Secretin-stimulated trypsin-like immunoreactivity in alcoholics.

Serum trypsin-like immunoreactivity (TLI) was studied in alcoholics without evidence of pancreatic disease and in controls. Basal values were 29 +/- 4.6 microgram/l (mean +/- S.E.M) in alcoholics and 23 +/- 4.4 microgram/l in controls (p not significant). The injection of secretin was followed by a significant increase of serum TLI in both groups; the integrated trypsin output (ITO) in the first hour after secretin administration was 947 +/- 403 (mean +/- S.E.M.) in alcoholics and 76 +/- 15 in controls (p less than 0.05). In 9 (75%) of the alcoholics tested, ITO was higher than the highest ITO of controls. The increase of serum TLI after injection of secretin is probably due to secretion and/or regurgitation of trypsinogen into the bloodstream when the pancreas is stimulated with intravenous secretin. In the light of experimental studies on chronic ethanol intoxication in animals, the increased ITO observed in alcoholics may suggest obstruction to pancreatic secretory flow in spite of the absence of any clinical sign of pancreatic disease.

Adult↗

Serum immunoreactive trypsin after secretin stimulation in chronic pancreatitis.

Serum immunoreactive trypsin (IRT) response to secretin injection was studied in 13 patients with chronic pancreatitis with different degrees of exocrine dysfunction and in 10 control subjects. The maximal increase of serum IRT from basal values and the integrated trypsin output (ITO) after secretin administration were significantly correlated with the output of chymotrypsin into the duodenum during caerulein-secretin infusion (p < 0.01), but not with the output of lipase nor of bicarbonate. Serum IRT response to secretin stimulation was greater in 4 of the 5 patients with chronic pancreatitis with mild to moderate exocrine dysfunction than in the control group, suggesting an increased regurgitation of IRT into the blood stream by the pancreas, probably due to some degree of obstruction to pancreatic secretory flow in absence of severe acinar cell damage. Conversely, the response of serum IRT after secretin administration in 7 of the 8 patients with severe exocrine pancreatic deficiency was lower than in control subjects, probably because of the advanced distruction of the acinar pancreatic tissue. The response of serum IRT to secretin stimulation seems to vary following pancreatic function impairment and might reflect the degree of pancreatic exocrine dysfunction in chronic pancreatitis.

Adolescent↗

Serum immunoreactive trypsin in type IV hyperlipoproteinemia.

Serum immunoreactive trypsin (IRT) under basal conditions and after pancreatic stimulation with secretin was studied in 10 patients with type IV hyperlipoproteinemia (HLP) and in 10 control subjects. No significant difference was observed between basal values of the two groups (p = NS). The increase of serum IRT was already significant 5 minutes after secretin administration (p < 0.01) and persisted with significance for one hour in both groups. The integrated trypsin output (ITO) was significantly greater in type IV HLP than in controls (510.3 +/- 17.8 and 72.2 +/ 17.6 respectively, mean +/- SEM, p < 0.0125). Only 2 (20%) of 10 patients with HLP had an ITO in the range of the controls. No significant correlation was found between ITO and triglyceride levels (p = NS). The response of serum IRT to secretin in HLP patients appears comparable to that observed in alcoholics and in patients with chronic pancreatitis with mild to moderate exocrine dysfunction, in whom there may be an abnormal regurgitation of trypsin-like material into the blood stream after secretin stimulation, probably due to an obstruction to pancreatic secretory flow. A similar obstructive mechanism may be hypothesized also in patients with HLP, but no data concerning the exocrine pancreatic secretion and the histological features of the pancreas are available to confirm this hypothesis.

Adult↗

Effect of cimetidine on trypsin-like immunoreactivity in serum.

Serum trypsin-like immunoreactivity (TLI) was studied after administration of secretin (GIH, 75 CU i.v.) in 10 alcoholics and in 3 patients with type IV hyperlipoproteinemia. A significant increase of TLI was observed after secretin administration and persisted throughout the test. In order to assess the possibility of an acid-sensitive effect, the test was repeated on a different day, one hour after the administration of cimetidine (400 mg. p.o.). Cimetidine did not affect serum TLI for one hour, but did reduce significantly the response of serum TLI to injection of secretin (p < 0.01). Some studies were performed, which failed to show any effect of cimetidine on pancreatic exocrine function. However, they were based on the measurement of pancreatic secretion into the duodenum, which required aspiration of gastric secretion from the stomach before entering the duodenum. Therefore, the reduction of TLI response to injection of secretin may be tentatively attributed to the inhibition of gastric acid secretion and delivery to the duodenum caused by cimetidine. If an endogenous acid-sensitive mechanism is involved, it is unlikely to be mediated by secretin.

Adult↗

Serum gastrin in chronic pancreatitis.

Fasting serum gastrin and gastrin response to a protein meal were measured in a group of patients with chronic pancreatitis and in controls. No significant differences were found between the two groups of subjects. In patients with chronic pancreatitis no relation was found between gastrin release and the severity of pancreatic exocrine insufficiency.

Adult↗