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Biomedical subjects

A Funakoshi

Publications and source records attributed to A Funakoshi.

At least 163 records · Page 9Linked to original sources
PubMed1990

Isolation and characterization of a tumor-derived human protein related to chromogranin A and its in vitro conversion to human pancreastatin-48.

A protein with pancreastatin-like immunoreactivity has been isolated and purified from liver metastasis of a patient with insulinoma. NH2-terminal residue analysis, in conjunction with the use of antibodies that are specific for the C-terminal amide peptide of porcine pancreastatin, identified this protein as a 186-amino-acid protein corresponding to human chromogranin A-116-301 (the fragment corresponding to the positions from 116 to 301 of human chromogranin A). Digestion of this protein with trypsin yielded a 48-amino-acid peptide with the retention of full pancreastatin activity. Serum from patient with insulinoma contains a peptide specie(s) that comigrates with the 48-amino-acid pancreastatin, suggesting that this peptide might be a physiologically important circulation form of pancreastatin in humans. A sensitive radioimmunoassay was established using antibody developed against a synthetic 29-amino-acid peptide amide of pancreastatin. Immunocytochemical staining revealed that a major population of human pancreatic islet cells were immunoreactive to the antiserum but with varying intensity of staining. Pancreastatin-like immunoreactivity was not observed in exocrine acinar cells.

Adenoma, Islet Cell↗
PubMed1990

Pancreastatin producing cell line from human pancreatic islet cell tumor.

It has been characterized that cell line QGP-1 derived from human non-functioning pancreatic islet cell tumor produces human pancreastatin. Exponentially growing cultures produced 5.7 fmol of pancreastatin/10(6) cells/hr. Human pancreastatin immunoreactivities in plasma and tumor after xenografting with QGP-1 into nude mouse were 92.7 fmol/ml and 160.2 pmol/g wet weight, respectively. Immunocytochemical study revealed both chromogranin A and pancreastatin immunoreactive cells in the tumor. Gel filtrations of culture medium and tumor extract identified heterogenous molecular forms of PST-LI which eluted as large and smaller molecular species. These results suggest that plasma pancreastatin levels may be useful as a tumor marker of endocrine tumor of the pancreas, and the pancreastatin producing cell line may be useful for studies of the mechanism of secretions and processing of chromogranin A and pancreastatin.

Adenoma, Islet Cell↗
PubMed1990

The importance of the C-terminal amide structure of rat pancreastatin to inhibit pancreatic exocrine secretion.

A C-terminal fragment of rat pancreatatin, a 26 residue peptide amide and a fragment without a C-terminal amide were synthesized by Fmoc-based solid phase methods and their biological activities were compared. The rat C-terminal fragment inhibited pancreatic exocrine secretions produced by the intravenous injection of 2-deoxy-D-glucose (a central vagal nerve stimulation), whereas the fragment without a C-terminal amide showed no effect on pancreas. These results indicate that the C-terminal amide of this peptide is necessary to reveal its biological activity.

Animals↗
PubMed1990

Rat pancreastatin inhibits both pancreatic exocrine and endocrine secretions in rats.

Effects of synthetic rat pancreastatin C-terminal fragment on both exocrine and endocrine pancreatic functions were examined in rats, in vivo and in vitro. Pancreastatin (20, 100 pmol, 1 nmol/kg/h) significantly inhibited CCK-8-stimulated pancreatic juice flow and protein output in a dose-related manner, in vivo. The inhibitory effect on bicarbonate output was not statistically significant. Pancreastatin did not significantly inhibit basal pancreatic secretions in vivo, and did not inhibit amylase release from the dispersed acini, in vitro. Insulin release stimulated by intragastric administration of glucose (5 g/kg) was significantly inhibited by pancreastatin (1 nmol/kg/h), in vivo. Plasma glucose concentrations were increased by pancreastatin infusion, but the increase was not statistically significant. Furthermore, pancreastatin inhibited insulin release from isolated islets, in vitro. Synthetic rat C-terminal pancreastatin fragment has bioactivities on both exocrine and endocrine pancreatic functions in rats.

Amylases↗
PubMed1990

Plasma pancreastatin responses after intrajejunal infusion of liquid meal in patients with chronic pancreatitis.

The plasma concentrations of pancreastatin and cholescystokinin (CCK), exocrine pancreatic responses, and gallbladder contraction following intrajejunal ingestion of 100 kcal/hr semidigested liquid meal (Clinimeal) were simultaneously studied in six controls and six patients with chronic pancreatitis. An intrajejunal infusion of Clinimeal resulted in significant rises of pancreastatin and CCK, which paralleled the pancreatic secretion and gallbladder contraction. On the other hand, an intrajejunal infusion of Clinimeal resulted in a delayed rise of pancreastatin and no rise of CCK in chronic pancreatitis. Pancreatic secretion did not increase, and gallbladder contraction was not induced in these patients. It is suggested that pancreastatin may play an important role in the regulation of intestinal phase of exocrine pancreas. The impaired pancreastatin and CCK release in chronic pancreatitis may be due to the inappropriate stimuli in the lumen, which is attributed to pancreatic exocrine dysfunction, or to disturbed physiological regulation between the pancreas and gastrointestinal tract.

Adult↗
PubMed1990

Inhibitory effect of pancreastatin on pancreatic exocrine secretions. Pancreastatin inhibits central vagal nerve stimulation.

The effects of the C-terminal fragment of rat pancreastatin on exocrine pancreatic secretions induced by several neural stimulations [IV injection of 75 or 15 mg/kg of 2-deoxy-D-glucose (central vagal nerve stimulation), injection of 2 mg of cisapride (proposed to elicit acetylcholine release from cholinergic nerve ending), and infusion of 1 or 3 mg.kg-1.h-1 of bethanechol (direct stimulation of acinar cells)] were examined in conscious rats. Rats with external bile and pancreatic fistulae were used. All the stimulations caused significant increases in pancreatic exocrine secretions. Pancreastatin at 100 pmol.kg-1.h-1 inhibited pancreatic secretions stimulated by IV injection of 2-deoxy-D-glucose but not those induced by the infusion of bethanechol or the injection of cisapride. Because these findings showed that pancreastatin inhibited pancreatic secretions induced by central vagal nerve stimulation, the effect of pancreastatin on cholecystokinin-stimulated pancreatic secretions in vagotomized rats was examined. Pancreastatin at 100 pmol.kg-1.h-1 did not inhibit pancreatic secretions stimulated by cholecystokinin octapeptide at 100 pmol.kg-1.h-1 in conscious rats after bilateral truncal vagotomy. These results suggest that pancreastatin inhibits pancreatic exocrine secretions by inhibiting vagal efferent nerve activity.

Animals↗
PubMed1990

Pancreastatin-like immunoreactivity in urine.

The concentration and molecular form of pancreastatin-like immunoreactivity (PST-LI) in urine of normal subjects and patients with noninsulin-dependent diabetes mellitus or chronic renal failure were examined. PST-LI output (mean +/- SEM) in urine of normal subjects was 74.6 +/- 8.5 pmol/day and 87.1 +/- 11.7 pmol/g creatinine. That in patients with noninsulin-dependent diabetes mellitus was 78.1 +/- 9.0 (SEM) pmol/day and 85.6 +/- 9.0 pmol/g creatinine and was not significantly different from that in normal subjects. Gel filtration analysis showed that PST-LI molecules excreted in urine of these two groups were smaller than human pancreastatin (43-52) (hPST-10) of C-terminal fragment. The PST-LI molecular forms were deduced to be nonbioactive from the result that hPST-10 did not inhibit pancreatic exocrine secretion. PST-LI excretion in patients with chronic renal failure was 258.5 +/- 62.9 pmol/day and 713.2 +/- 219.6 pmol/g creatinine. A molecular form corresponding to hPST-52 and a larger form eluted in the high mol wt region (approximately mol wt 15 K) were detected by gel filtration of urine from these patients, indicating that PST-LI is excreted in urine without degradation in patients with chronic renal failure. These results support the suggestion that the kidney may play an important role in PST degradation or metabolism.

Chromatography, Gel↗
PubMed1990

Necessity of hyperglycemia for effects of endogenous cholecystokinin on insulin and pancreatic exocrine secretion in conscious rats.

The effects of endogenous cholecystokinin (CCK) on insulin and pancreatic exocrine secretion were examined in conscious rats. Rats with bile and pancreatic fistulae, one duodenal cannula, and two jugular vein cannulae were divided into four groups, with and without glucose infusion (0.2 g/(ml.h)), and with bile and pancreatic juice (BPJ) diversion and return. Without glucose infusion, BPJ diversion did not have any significant effect on the plasma level of insulin or glucose; but with glucose infusion, it caused a significant increase in plasma insulin concentration 1 h after the diversion. The plasma glucose concentrations in the groups with BPJ diversion and return were not significantly different, and the response of pancreatic exocrine secretion to BPJ diversion was suppressed slightly, but not significantly, by glucose infusion. The plasma CCK concentration was increased significantly by BPJ diversion, but not affected by glucose infusion. These results indicate that, as observed in in vitro experiments with exogenous CCK, in conscious rats, endogenous CCK stimulates both exocrine and endocrine secretion of the pancreas, and that hyperglycemia is necessary for these effects to become apparent.

Animals↗
PubMed1990

[Effects of unilateral temporal lobectomy on verbal dichotic listening test].

Verbal dichotic listening test was conducted before and after anterior temporal lobectomy on 25 patients who underwent the operation because of their medication-resistant epileptic seizures. Their speech dominance by Wada test was all left sided. 1. Preoperatively, patients having the epileptogenic focus in the right temporal lobe (R-TLE) and those having the focus in the left (L-TLE) were, as expected, all right-ear dominant. The mean number of correct responses was fewer in L-TLE than in R-TLE group. 2. Postoperatively, no detrimental effects for recognition of verbal auditory stimuli by the ear contralateral to the focus was observed both in L-TLE and in R-TLE group. 3. Postoperatively, the ear-dominance shifted: to the left in patients with L-TLE, and to the right more conspicuously in patients with R-TLE compared to the preoperative scores. In other words, the recognition ability by the ears ipsilateral to the side of focus, or of resected temporal lobe, was ameliorated. Summarizing, the unilateral anterior temporal lobectomy did not cause "lesion effect" but yielded improvement of verbal auditory recognition by ears ipsilateral to the epileptogenic focus. Diminished epileptic bombardment resulted in by the resection surgery may be a possible explanation.

Adult↗
PubMed1990

Prognosis of pancreatic endocrine function in chronic pancreatitis: significance of surgical treatment.

Of 100 cases of chronic pancreatitis, 20 received surgical treatment. The duration of illness before surgical treatment was less than 5 years in 75% of patients. Post-operatively, the persistent abdominal pain was relieved and serum pancreatic enzyme levels were normalized in all the patients except two who continued drinking alcohol. Exocrine and endocrine pancreatic function were unchanged or slightly improved post-operatively in most cases. In 9 of 10 patients who have been followed up post-operatively for over 4 years, pancreatic endocrine function has been maintained by diet control with no significant impairment of glucose tolerance. These results suggest that in patients with chronic pancreatitis surgical intervention is of greatest benefit in preservation of pancreatic functions when it is performed at an early stage in which these functions are relatively well maintained.

Chronic Disease↗
PubMed1989

Isolation and characterization of a tumor-derived human pancreastatin-related protein.

A protein with pancreastatin-like immunoreactivity has been isolated and purified from liver metastasis of a patient with insulinoma. NH2-terminal sequence analysis in conjunction with the use of antibodies specific for the C-terminal structure of pancreastatin identified this protein as a 186-amino acid residue protein corresponding to human chromogranin A-116-301. Using a sensitive radioimmunoassay it was found that serum from the patient with insulinoma contains two peptide species; one comigrates with the 186-amino acid residue pancreastatin and the other the 48-residue pancreastatin.

Amino Acid Sequence↗
PubMed1989

Bioactivity of human pancreastatin and its localization in pancreas.

Synthetic human pancreastatin and its C-terminal fragment were first evaluated with respect to the biological activity on the insulin secretion in the isolated rat islets. Both these pancreastatins inhibited glucose-stimulated insulin secretion at a concentration of 100 nM. The relative molar potency of human pancreastatin compared to that of porcine pancreastatin was equivalent. The pancreastatin-reactive cells were widely located in the islets of Langerhans, and not observed in exocrine acinar cells by immunocytochemistry using human pancreastatin C-terminal specific antibody. These results suggest that human pancreastatin may modulate endocrine function of the pancreas, especially insulin secretion.

Amino Acid Sequence↗
PubMed1989

Bioactivity of synthetic C-terminal fragment of rat pancreastatin on endocrine pancreas.

A C-terminal fragment of rat pancreastatin, 26-residue peptide amide was synthesized by the Fmoc-based solid phase method and its biological activity was evaluated for the first time in the conscious rat. Rat pancreastatin inhibited glucose-stimulated insulin secretion and elevated blood glucose levels in a concentration of 10 nmol/kg/h. The relative molar potency of that of porcine is equivalent. This study suggests that the synthetic rat pancreastatin has a biological activity, and may play a physiological role in the endocrine pancreas.

Animals↗
PubMed1989

Involvement of pancreatic polypeptide (PP) in luminal feedback regulation in the conscious rat.

The possibility of the involvement of pancreatic polypeptide (PP) release in luminal feedback regulation in the conscious rat was examined. Pancreatic secretion in the intestinal phase in the rat is regulated by negative feedback control so that a decrease in luminal protease activities produced by a diversion of bile-pancreatic juice (BPJ) from the intestine stimulates pancreatic secretion. Plasma concentration of rat PP and the effect of exogenous infusion of rat PP on pancreatic secretions during BPJ diversion were determined. Plasma PP concentration significantly increased with BPJ diversion and peaked at 90 min after BPJ diversion began, almost paralleling changes in protein output. Exogenous PP infusion (1, 2 and 10 micrograms/kg/hr) inhibited pancreatic protein and fluid outputs but not the bicarbonate output during BPJ diversion. PP was shown to be physiologically released in the intestinal phase of pancreatic secretion; however, the physiological role of endogenous PP remains unknown.

Animals↗
PubMed1989

Effects of synthetic human gastrin-releasing peptide on pancreatic exocrine secretion and release of pancreatic polypeptide in conscious rats.

The effects of a newly synthesized peptide, human gastrin-releasing peptide (hGRP), on the pancreatic exocrine secretion and the release of pancreatic polypeptide (PP) were examined in the conscious rat. Plasma PP concentrations were determined by a recently established specific radioimmunoassay for rat PP. Amounts of 0.18, 0.35, and 3.5 nmol/kg/h hGRP significantly stimulated both pancreatic exocrine secretion and 0.35 nmol/kg/h of hGRP increased PP release. Simultaneously infused proglumide (300 mg/kg/h) did not affect either pancreatic exocrine secretion or PP release. However, simultaneous infusion of atropine (100 micrograms/kg/h) slightly inhibited PP release, but did not restrict the incremental response of pancreatic protein secretion to hGRP. These results suggest that hGRP directly stimulates pancreatic exocrine secretion and PP release.

Animals↗
PubMed1989

High plasma pancreastatinlike immunoreactivity in a patient with malignant insulinoma.

High levels of pancreastatinlike immunoreactivity were detected in the plasma (2.9 pmol/ml, greater than 200-fold the normal level), pancreas (2.9 nmol/g wet wt, greater than 450-fold the normal level), and liver (1.6 nmol/g wet wt) of a patient with pancreatic insulinoma with metastasis to the liver by a sensitive and specific radioimmunoassay for human pancreastatin. Antiserum was produced against the C-terminal fragment of human pancreastatin-(24-52), which was synthesized according to the sequence of human chromogranin A corresponding to that of pancreastatin. With the antiserum, intense immunocytochemical staining was detected in the tumors. Sephadex G-50 gel filtration showed that the tumors and plasma contained two molecular forms of pancreastatinlike immunoreactivity--a molecular form coeluted with synthetic human pancreastatin-52 and a larger molecular form (Mr approximately 12,000-15,000). The smaller form eluted in the same position as synthetic human pancreastatin-52 on reverse-phase high-performance liquid chromatography.

Adenoma, Islet Cell↗