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Biomedical subjects

A Funakoshi

Publications and source records attributed to A Funakoshi.

At least 127 records · Page 7Linked to original sources
PubMed1993

Simultaneous determinations of pancreatic phospholipase A2 and prophospholipase A2 in various pancreatic diseases.

Pancreatic phospholipase A2 (PLA2) is secreted into the pancreatic juice by pancreatic acinar cells as a proenzyme (proPLA2), which is activated by trypsin. Radioimmunoassays with monoclonal antibodies to PLA2 and proPLA2 were used to examine the serum PLA2 and proPLA2 levels simultaneously in patients with various pancreatic diseases. In healthy subjects, proPLA2 proved to be the major form of the enzyme. The serum PLA2 level were found to be significantly increased in patients with acute pancreatitis, the active phase of chronic relapsing pancreatitis, and the early stage of pancreatic cancer. In the terminal stage of pancreatic cancer the serum PLA2 level became low. In patients with chronic pancreatitis, significant correlations were observed between the levels of factors evaluated by the secretin test and the serum total PLA2 and proPLA2 level, but not the PLA2 level. The serum PLA2 and proPLA2 concentrations, and the proportion of proPLA2 in the total, were within normal ranges in patients with liver cirrhosis, hepatocellular carcinoma, and chronic renal failure. These results suggest that simultaneous measurements of serum PLA2 and proPLA2 are clinically useful for diagnosis and monitoring of the active phase of pancreatitis.

Acute Disease↗
PubMed1993

Regulation of intestinal concentration of cholecystokinin by bile and/or pancreatic juice.

Pancreatic exocrine secretion in conscious rats is regulated by intraluminal bile and/or pancreatic juice. Exclusion of bile and/or pancreatic juice from the intestinal lumen caused cholecystokinin (CCK) release and stimulated pancreatic secretion. CCK in the plasma is mainly derived from endocrine cells in the proximal small intestinal mucosa. We examined the changes in CCK concentrations in the intestinal mucosa and compared them to those of plasma CCK concentrations and the changes of luminal trypsin activities after bile and/or pancreatic juice diversion in conscious rats. Rats with bile and pancreatic fistulae were used. Each treatment of bile, pancreatic juice, and bile-pancreatic juice diversion decreased luminal trypsin activity and increased plasma and intestinal CCK concentrations. The potency of the stimulatory effect on plasma and intestinal CCK concentrations was bile-pancreatic juice diversion > pancreatic juice diversion > or = bile diversion. Neither plasma CCK concentration nor intestinal CCK concentration was in inverse proportion to trypsin activity. The plasma CCK concentration did not parallel intestinal CCK concentration. Intravenous infusion of CCK-8 (300 pmol/kg/hr) did not increase CCK concentration in the intestinal mucosa. It was proposed that bile and/or pancreatic juice in the intestinal lumen regulated CCK concentrations not only in the plasma but also in the intestinal mucosa.

Animals↗
PubMed1993

Two mechanisms of inhibition by bile on luminal feedback regulation of rat pancreas.

BACKGROUND: Pancreatic exocrine secretion in conscious rats is regulated by luminal protease activities. A decrease in protease activities results in pancreatic hypersecretion (luminal feedback regulation). Although bile has been known to affect this regulation, the mechanism is not clear. In the present study, the effect of bile in the intestinal lumen on luminal feedback regulation was examined. METHODS: Rats were prepared with separate cannulas for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. Because the rate of enzyme secretion varies in individual rats, porcine trypsin was infused instead of pancreatic juice. Graded doses of porcine trypsin were infused with bile or Tris buffer containing 10 mmol/L CaCl2 instead of bile. RESULTS: The trypsin activities in the proximal quarter of the small intestine were similar in rats infused with bile and with Tris buffer containing 10 mmol/L CaCl2 (without bile); however, increments of pancreatic secretions of fluid and protein were significantly higher in rats without bile infusion than in those with bile infusion. Infusion of calcium-free Tris buffer resulted in significantly lower trypsin activity. CONCLUSIONS: The results indicate that bile has two inhibitory mechanisms on pancreatic secretion, one stabilizing luminal trypsin, the other independent of luminal trypsin activity.

Animals↗
PubMed1993

Diabetogenic effects of FK506 on renal subcapsular islet isografts in rat.

Previously we demonstrated prevention of immune rejection in rat islet allografts by continuous subcutaneous (s.c.) administration of FK506 and also showed that FK506 might have diabetogenic effects (Ryu and Yasunami (1991) Transplantation, 52, 599-605). The purpose of the present study was to characterize further diabetogenic effects of FK506 on renal subcapsular islet isografts in rat. Continuous s.c. administration of FK506 (3 mg/kg/day) for 35 days produced glucose intolerance in the recipients as demonstrated by intravenous (i.v.) glucose tolerance test at the end (35 days) and after discontinuation (90 days) of FK506 administration. Morphologically, beta cells in the grafts of FK506-treated group were degranulated at 35 and 120 days after transplantation. Electron microscopically, degranulation, marked swelling of rough endoplasmic reticulum, Golgi apparatus and mitochondria were detected in beta cells of the grafts treated with FK506 at 35 days, and at 120 days there was moderate structural recovery in the organella. These findings clearly demonstrate that FK506 has diabetogenic effects on renal subcapsular islet isografts in rat and also suggests potential reversibility of damages by FK506 in beta cells of the grafts.

Animals↗
PubMed1993

Comparison of plasma pancreastatin and GAWK concentrations, presumed processing products of chromogranin A and B, in plasma of patients with pancreatic islet cell tumors.

Plasma pancreastatin (PST) and GAWK, peptides processed from chromogranin A and B, were elevated in patients with various neuroendocrine tumors. In the present study, we measured plasma PST- and GAWK-like immunoreactivity (LI) concentrations in 12 patients with pancreatic islet cell tumors and evaluated them as a marker for these tumors. We also performed the gel filtration of the plasma from a gastrinoma patient and investigated the processing of PST and GAWK in plasma. Elevation of plasma PST-LI was found in 4 of 12 patients (33%) and elevation of plasma GAWK-LI was found in 6 of 12 patients (50%). A significant correlation was not found between plasma PST- and GAWK-LI concentrations of the patients. In the gel permeation chromatography of the plasma from a gastrinoma patient, PST-LI composed of a single peak but GAWK-LI composed of several components with wide range molecular weights.

Adenoma, Islet Cell↗
PubMed1993

Parallel secretion of pancreastatin and somatostatin from human pancreastatin producing cell line (QGP-1N).

In this investigation we studied pancreastatin (PST) secretion from a human PST producing cell line (QGP-1N) in response to various secretagogues. Immunocytochemical study revealed the immunoreactivity of PST and somatostatin (SMT) in the same cells of a monolayer culture. Ki-ras DNA point mutation on codon 12 was found. Carbachol stimulated secretion of PST and SMT and intracellular Ca2+ mobilization in the range of 10(-6)-10(-4) M. The secretion and Ca2+ mobilization were inhibited by atropine, a muscarinic receptor antagonist. Phorbol ester and calcium ionophore (A23187) stimulated secretion of PST and SMT. The removal of extracellular calcium suppressed both secretions throughout stimulation with 10(-5) M carbachol. Fluoride, a well-known activator of guanine nucleotide binding (G) protein, stimulated intracellular Ca2+ mobilization and secretion of PST and SMT in a dose-dependent manner in the range of 5-40 mM. Also, 10(-5) M carbachol and 20 mM fluoride stimulated inositol 1,4,5-triphosphate production. However, cholecystokinin and gastrin-releasing peptide did not stimulate Ca2+ mobilization or secretion of the two peptides. These results suggest that secretion of PST and SMT from QGP-1N cells is regulated mainly by acetylcholine in a parallel fashion through muscarinic receptors coupled to the activation of polyphosphoinositide breakdown by a G-protein and that increases in intracellular Ca2+ and protein kinase C play an important role in stimulus-secretion coupling.

Adenoma, Islet Cell↗
PubMed1993

[Postictal aphasia and its generating mechanism in 3 patients with localization-related epilepsy].

Semiology of postictal aphasia as well as its generating mechanism involving both the epileptogenic zone and language area has not yet been sufficiently elucidated. Therefore, postictal aphasias were studied in 3 patients with localization-related epilepsy. Postictal motor aphasia was observed in a patient (patient 1) with frontal lobe epilepsy whose recovery of language function progressed from loss of language function, to Broca's aphasia, and eventually to poor spontaneous speech. Postictal sensory aphasia was observed in 2 patients (patient 2 and 3) with temporal lobe epilepsy whose recovery of language function progressed from loss of language function, to jargon, and eventually to circumlocutory anomic speech. Both patient 2 and 3 did not show fluent speech. Seizure manifestations, EEG, IMP-SPECT and MRI indicated that epileptogenic zones were in the left frontal lobe including Broca's area in patient 1, the mesial part of the left temporal lobe in patient 2, and the middle and posterior part of the left temporal lobe including Wernicke's area in patient 3. A postictal verbal dichotic listening test showed the reduction of correct responses by right ear in the patient 3. Postictal auditory verbal learning tests showed the impairment of verbal memorization in patient 2 and 3. The impairment of verbal memorization was particularly marked in patient 2. These results suggest that 1) the characteristics of postictal motor and sensory aphasia are clearly elucidated by analyzing the sequence of recovery from postictal language dysfunction, 2) postictal aphasia is generated by the epileptogenic zone involving the language area or the ictal discharges propagating to the language area, and 3) not only the disturbance of language function, but also the impairment of verbal memorization seems to participate in the disturbance of repeating and understanding sentences in the patient with postictal sensory aphasia.

Adult↗
PubMed1993

[Long-term follow-up of a case of Landau-Kleffner syndrome].

Long-term investigation of a male case of Landau-Kleffner syndrome with auditory, verbal and non-verbal agnosia was performed clinico-electroencephalographically and neuropsychologically. Atypical absences and secondarily generalized tonic-clonic seizures were observed. The spike-wave index of slow wave sleep from all-night EEG recordings was 96% in this case. It was impossible to differentiate this case from epilepsy with "continuous spikes and waves during slow wave sleep (CSWS)" except the presence of auditory agnosia. Auditory agnosia of this case disappeared after antiepileptic therapy. It is suggested that Landau-Kleffner syndrome showing CSWS may have a good prognosis about agnosia from that of this case and others previously reported.

Agnosia↗
PubMed1992

Interaction between phosphoinositide turnover system and cyclic AMP pathway for the secretion of pancreastatin and somatostatin from QGP-1N cells.

It is found that secretion of pancreastatin and somatostatin from QGP-1N cells is regulated through muscarinic receptor-mediated activation of phosphatidylinositide hydrolysis system. In this report, whether the cAMP pathway interacts with the phosphoinositide turnover system for the secretion of pancreastatin and somatostatin from QGP-1N cells through muscarinic receptors was studied. Stimulation of QGP-1N cells with carbachol increased intracellular cAMP levels. The carbachol-induced increase in cAMP levels was inhibited by atropine. Calcium ionophore (A23187) and phorbol 12-myristate 13-acetate increased cAMP synthesis. Dibutyryl cAMP, forskolin and theophylline stimulated secretion of pancreastatin and somatostatin. When either dibutyryl cAMP, forskolin or theophylline was added in culture medium with A23187, phorbol ester or carbachol, a synergistic effect was found on pancreastatin and somatostatin secretion. These results suggest that interaction between the phosphoinositide turnover system and the cAMP pathway occurs in QGP-1N cells through muscarinic receptor stimulation for the secretion of pancreastatin and somatostatin.

Adenoma, Islet Cell↗
PubMed1992

Stimulatory effects of islet amyloid polypeptide (amylin) on exocrine pancreas and gastrin release in conscious rats.

A rat islet amyloid polypeptide (amylin), 37-residue peptide amide was synthesized by the Fmoc-based solid phase method and the biological activity of synthetic rat amylin on exocrine pancreas was evaluated for the first time in conscious rat. Amylin (1, 10 nmol/kg/h) stimulated pancreatic exocrine secretion and plasma gastrin concentration. CR-1409, a CCK receptor antagonist, did not change amylin-stimulated pancreatic secretion. However, omeprazole (proton pump inhibitor) and atropine inhibited amylin-stimulated pancreatic secretion. This study suggests that amylin may play a role in biological action in the exocrine pancreas possibly mediated by gastric acid hypersecretion.

Amyloid↗
PubMed1992

Pertussis toxin non-sensitive G protein mediates cholinergic stimulation for secretion of pancreastatin and somatostatin from QGP-1N cells.

To clarify the possible role of a guanine nucleotide-binding protein (G-protein) in the signal transducing system activated by carbachol, actions of carbachol on human pancreastatin producing cell line (QGP-1N) were compared with those of fluoride, a well-known activator of stimulatory (Gs) or inhibitory (Gi) G protein. 10(-5) M of carbachol as well as 20 mM of NaF stimulated secretion of pancreastatin and somatostatin and intracellular Ca2+ mobilization. These secretion and Ca2+ mobilization were not modified by pertussis toxin, an inhibitor of Gi protein. These results suggest that pancreastatin and somatostatin secretions from QGP-1N are regulated by acetylcholine through a muscarinic receptor coupled to the activation of polyphosphoinositide breakdown by a G protein, which appears to be fluoride sensitive but is other than a Gi-like protein.

Calcium↗
PubMed1992

Changes in plasma and duodenal cholecystokinin concentrations after pancreatic duct occlusion in rats.

The changes in plasma and duodenal cholecystokinin (CCK) concentrations after pancreatic duct occlusion were examined in rats. The rats were sacrificed 1, 3, 7, 10, 14, and 30 days after occlusion of the duct. Histological examination showed acute inflammation on days 1 and 3 after duct occlusion, interstitial fibrosis and regenerative changes on days 7, 10, and 14, and pancreatic atrophy on day 30. The plasma CCK concentration increased from 0.45 pM to 2.0 pM after the occlusion and then remained high throughout the observation period. In contrast to the stable increase in plasma CCK concentration, the CCK content in the duodenum increased on days 1 and 3, decreased on day 7, increased on day 10, reaching over the control level on day 14, and then returned to the control level on day 30. Administration of boiled and 10-fold concentrated rat pancreatic juice or human pancreatic secretory trypsin inhibitor for seven days after pancreatic duct occlusion reversed the decrease in duodenal CCK content. The major molecular forms of duodenal CCK were CCK-8, -33, and -58. These results indicate that (1) basal plasma CCK concentration did not reflect the duodenal CCK content, (2) duodenal CCK content was well correlated with a decrease in inflammation in the pancreas, and (3) a nonenzymatic component in the pancreatic juice reversed the decrease in duodenal CCK content and body weight caused by pancreatic duct occlusion.

Acute Disease↗
PubMed1992

Growth inhibition of human pancreatic cancer cells by cholecystokinin receptor antagonist in tissue culture and in nude mice.

The Human pancreatic carcinoma cell line KP-1N and its clone KP-1NL which has a high rate of liver metastasis were established. Ki-ras DNA point mutation on the codon 12 was found. The growth of KP-1N was stimulated by a physiological range of concentration (10(-11)-10(-10) M) of cholecystokinin and the increase was inhibited by the addition of a cholecystokinin receptor antagonist (CR 1505). Daily injections of CR 1505 (35 mg/kg) diminished the number of tumor colonies in the liver that were formed after an intrasplenic injection of the highly liver metastatic KP-1NL cells. These results suggest that cholecystokinin antagonists may be useful as growth inhibitors for some pancreatic cancer.

Adenocarcinoma↗
PubMed1992

Isolation and bioactivity of putative cholecystokinin-releasing peptide from rat small intestinal mucosa.

Pancreatic exocrine secretion in the conscious rat is regulated by proteases in the intestine secreted by the pancreas, and cholecystokinin (CCK) is known to be involved in the mechanism. The authors proposed that the release of CCK was regulated by a CCK-releasing factor secreted into the intestinal lumen from the proximal intestine. We isolated and partially purified a CCK-releasing factor from rat small intestine by gel filtration and high performance liquid chromatography. The partially purified CCK-releasing factor increased pancreatic exocrine secretions and plasma CCK concentrations in conscious rats and this activity was abolished after the incubation with trypsin. The bioactivity of the partially purified CCK-releasing factor was confirmed.

Animals↗
PubMed1992

Stimulatory and inhibitory effects of bile salts on rat pancreatic secretion.

The effects of various species of bile salts (chenodeoxycholate, deoxycholate, ursodeoxycholate and cholate, and their taurine and glycine conjugates) on pancreatic exocrine secretion were studied in conscious rats with external bile and pancreatic fistulae. For examination of the stimulatory effects of bile salts, bile and pancreatic juice were collected for a basal period of 90 minutes and returned to the intestine, and then solutions of bile salts (60 mmol/L) were infused intraduodenally at a rate of 1 mL/h for 2 hours. For examination of their inhibitory effects, pancreatic secretion was stimulated by exclusion of the bile and pancreatic juice; and then solutions of the bile salts were again infused intraduodenally. Chenodeoxycholate, glycochenodeoxycholate, ursodeoxycholate, deoxycholate, and its conjugates (glycodeoxycholate and taurodeoxycholate) significantly increased the fluid, bicarbonate and protein outputs, and bicarbonate concentration, with decrease in protein concentration. These increases were partially inhibited by infusion of either a cholecystokinin antagonist or secretin antibody. In contrast, cholate, taurocholate, tauroursodeoxycholate, glycoursodeoxycholate, and taurochenodeoxycholate inhibited pancreatic secretion and increase in the plasma cholecystokinin concentration produced by exclusion of bile and pancreatic juice. Thus, some bile salts, including taurocholate and taurochenodeoxycholate (major bile salts in rat bile) inhibited pancreatic secretion and cholecystokinin release, whereas some other bile salts increased pancreatic secretion via cholecystokinin release and secretin release.

Animals↗
PubMed1992

Degradation of human pancreastatin-52 by human kidney extract.

We examined the in vitro degradation of human pancreastatin-52 (hPST-52) and a larger molecular form (approximate 15 kDa) of human PST by an enzyme extract from human kidney. The PST-degrading activity was determined from the amount of immunoreactive PST remaining after incubation of hPST-52 or the larger molecular form with the enzyme extract. Human PST-52 was degraded to smaller molecular forms within 30 min, but the larger molecule was not degraded within 90 min. Phosphoramidon, an inhibitor of endopeptidase, metal ion chelators (EDTA and 1, 10-phenanthroline) and Cu2+ prevented the degradation of hPST-52. These results indicated that the enzyme in the kidney extract degraded hPST-52 and smaller forms of the peptide, but had no effect on the 15 kDa form.

Chromatography, Gel↗
PubMed1992

Effect of taurocholate on CCK release and pancreatic secretion produced by two CCK-releasing peptides in conscious rats.

The role of luminal bile salts (taurocholate) in regulation of rat pancreatic secretion was examined by studies on the effects of luminal stimulants on the pancreas during infusion of various concentrations of taurocholate into the duodenum of conscious rats. Rats with external bile and pancreatic fistulae were used. For 24 h before the experiment, pancreatic juice was excluded from the intestine but bile was continuously returned to the duodenum. From the beginning of the experiment, 8-200 mM of taurocholate was infused at a rate of 1 ml/h instead of returning the bile. Pancreatic juice was collected for a 2-h period and then 2 micrograms of pancreatic secretory trypsin inhibitor-61 (PSTI-61) (= monitor peptide) or partially purified putative CCK-releasing peptide from rat intestine (intestinal CCK-RP) was injected into the duodenum (1 ml/min). Continuous infusion of taurocholate maintained a constant rate of pancreatic secretion, except at a concentration of 8 mM, which resulted in a slight increase in pancreatic secretion. Both PSTI-61 and intestinal CCK-RP significantly increased pancreatic secretions during infusion of 20 or 40 mM taurocholate, but had no significant effect during infusion of 80 or 200 mM taurocholate. Therefore, higher concentrations of taurocholate in the intestine prevented the stimulatory effects of luminal stimulants, probably by preventing the latter from reaching CCK cells.

Animals↗