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Biomedical subjects

S Funakoshi

Publications and source records attributed to S Funakoshi.

At least 55 records · Page 3Linked to original sources
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

Effects of corticostatin-I on rat adrenal cells in vitro.

We have examined the mechanism by which corticostatin-I (CS-I) acts to attenuate ACTH-induced steroidogenesis in rat adrenal cells. CS-I inhibited ACTH-induced corticosterone production in a dose-dependent manner, without any effects on the basal corticosterone level in adrenal cells. When the cells were stimulated by 100 pg ACTH/ml, the minimum effective concentration of CS-I was 100 ng/ml, and 0.3-1.0 micrograms CS-I/ml produced a 50% reduction of the stimulated corticosterone production. The inhibitory effect of CS-I on ACTH-stimulated corticosterone production became apparent within 15 min of incubation, and the effect was reversed quickly by the removal of CS-I from the media. CS-I had no effect on angiotensin II-stimulated aldosterone production by adrenal zona glomerulosa cells. CS-I also did not affect cyclic AMP- or forskolin-stimulated corticosterone production. In an in-vitro binding study using 125I-labelled CS-I, CS-I showed considerable specific binding to rat adrenal cells, and the binding competed with ACTH in a dose-dependent manner. These experiments suggest that CS-I competes with ACTH on their binding sites and exerts an inhibitory effect on the adrenal cells.

Adrenal Glands↗
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

[Adjuvant chemotherapy for stage I and II non-Hodgkin's lymphoma--a seven-year follow up].

From 1975 to 1983, 51 patients of stage I (30) and II (21) of non-Hodgkin's lymphoma were treated with a combination chemotherapy consisting of vincristine, cyclophosphamide and prednisolone as an adjuvant therapy after radiation or operation. The following results were obtained. 1) Nine patients in stage I and 7 in stage II relapsed, so that 10 year-relapse free survival rates were 68% in stage I and 67% in stage II, respectively. 2) Three patients in nodal lymphomas, 7 in Waldeyer's ring lymphomas and 6 in extranodal lymphomas relapsed, so that 10 year-relapse free survival rates were 80%, 48% and 72%, respectively. 3) Ten year-survival rates were 86% in stage I and 70% in stage II. 4) Ten year-survival rates were 82% in nodal lymphomas, 62% in Waldeyer's ring lymphomas and 86% in extranodal lymphomas. 5) Ten patients relapsed within 1 year, 4 between 1-5 years and 2 after 5 years. Relapses occurred in other than primary sites in most patients. These results suggest that an adjuvant chemotherapy is useful for localized non-Hodgkin's lymphoma, but more intensive chemotherapy before local treatments is necessary.

Adult↗
PubMed1989

Magainin 1-induced leakage of entrapped calcein out of negatively-charged lipid vesicles.

Effects of magainin 1, a novel antimicrobial peptide, on the permeability of lipid vesicles were investigated by using calcein as a trapped fluorescent marker. Magainin 1 induces the leakage of calcein specifically out of negatively-charged vesicles. The peptide binds to bovine brain phosphatidylserine sonicated vesicles according to the Langmuir isotherm with a binding constant of 3.8.10(5) M-1 and a binding-site number of 0.10 per lipid molecule. The leakage seems to occur at a critical binding number of approx. 0.03 per lipid molecule. A circular dichroism study revealed that magainin 1 conforms mainly to an unordered structure both in an aqueous solution and in the presence of egg yolk phosphatidylcholine vesicles, whereas to an amphiphilic helix with the phosphatidylserine vesicles. In conclusion, magainin 1 interacts with acidic lipids through electrostatic interactions followed by hydrophobic interactions to form an amphiphilic helix, inducing the leakage.

Animals↗
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

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↗
PubMed1989

Inactivation and elimination of viruses during the fractionation of an intravenous immunoglobulin preparation: liquid heat treatment and polyethylene glycol fractionation.

A method for the heat treatment of human IgG solution at 60 degrees C for 10 h was established. Human immunodeficiency, mumps, vaccinia and 4 other viruses were added to the IgG solution in 33% sorbitol and heated at 60 degrees C. Those viruses were inactivated within 1 h. Heat-treated intravenous IgG (IVIG-H) was prepared by heat treatment and polyethylene glycol (PEG) fractionation. Conventional nonheated intravenous IgG (IVIG-C) was prepared from the same source paste by the fractionation method. No physicochemical or biological difference was observed between the heated and control IVIG preparations.

Animals↗
PubMed1989

Plasma pancreastatin-like immunoreactivity in various diseases.

Plasma pancreastatin (PST)-like immunoreactivity in normal subjects and patients with various diseases was estimated by a RIA, using antiserum raised against a synthetic C-terminal peptide of human PST deduced from the sequence of human chromogranin-A. The mean level +/- SEM was 13.2 +/- 0.6 pmol/L in normal subjects, but was significantly higher in patients with chronic renal failure (526.7 +/- 48.5). An immunoreactive form corresponding to a human PST-like sequence [human chromogranin-A-(250-301)] and a larger form were detected by gel filtration of plasma from these patients, suggesting accumulation of the larger molecular form in these patients. A significant increase in PST-like immunoreactivity was also found in patients with liver cirrhosis (20.8 +/- 3.0 pmol/L), but not in patients with noninsulin-dependent diabetes mellitus, chronic pancreatitis, or pancreatic cancer. Elevated levels were found in 16 of the 21 patients with small cell lung carcinoma examined. High levels were also found in 3 of 11 patients with islet cell tumor.

Adenoma, Islet Cell↗
PubMed1989

Protease-catalyzed semisynthesis of human neuropeptide Y.

Human neuropeptide Y was semisynthesized by enzymatic condensation of des-Tyr36-NH2 human neuropeptide Y and H-Tyr-NH2 using Pseudomonas aeruginosa elastase, a metalloenzyme possessing a hydrolytic specificity for the imino side of hydrophobic amino acids. The optimum pH for this enzymatic synthesis was judged to be around 7 in a high concentration of an organic solvent.

Amino Acid Sequence↗
PubMed1989

Comparative effects of mammalian pancreastatins on the pancreatic exocrine secretion.

We have reported that porcine pancreastatin inhibits cholecystokinin (CCK)-stimulated pancreatic exocrine secretion in conscious rats. In the present study, the effects of mammalian pancreastatins on exocrine pancreatic functions in rats were compared using synthetic pancreastatins (porcine, bovine, human, and rat). Rats were prepared with cannulae draining pure pancreatic juice and bile separately and a duodenal cannula to return bile-pancreatic juice to the intestine and with a jugular vein cannula. After 90-min basal collection of pancreatic juice, CCK-8 (100 pmol/(kg.h] was infused for 3 h with or without pancreastatins (100 pmol/(kg.h]. All pancreastatins significantly inhibited protein output at an equivalent molar potency. These results suggest that mammalian pancreastatins have the same biological activity of a comparable magnitude and exert a similar biological action on the exocrine pancreas.

Amino Acid Sequence↗
PubMed1988

Bioactivity of synthetic human pancreastatin on exocrine pancreas.

A biological activities of synthetic human pancreastatin (1-52) and its C-terminal fragment (24-52) were evaluated for the first time in the conscious rats. Both pancreastatins inhibited CCK-stimulated pancreatic secretion in a range of 20-200 pmol/kg/h with the same potency, indicating that the C-terminal portion of this peptide has a full biological activity. The relative molar potency of this substance compared to that of porcine pancreastatin was equivalent. This study suggests that human pancreastatin has the same biological activity as that of porcine, and plays a biological action in the exocrine pancreas.

Animals↗
PubMed1988

Studies on peptides CLVIII. Model experiments for the synthesis of open-chain unsymmetrical cystine-peptides.

Treatment of a mixture of Cys(R)(O) and Cys(R') with an acid was found to generate cystine in fairly good yields, when suitable R, R', and an acid were selected. An unsymmetrical cystine peptide was prepared by treatment of a mixture of Z(OMe)-Cys(R) (0)-Ala-NH2 (R = Acm or MBzl) and Z(OMe)-Cys(MBzl)-Gly-OBzl with TFA or 1 M TFMSA/TFA3. Oxytocin was obtained in an excellent yield by TFA treatment of the protected peptide containing Cys(Acm)(0) and Cys(MBzl). Thus, formation of the disulfide bond was found feasible at the position of Cys(R) (0).

Cystine↗