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T Oka

Publications and source records attributed to T Oka.

At least 1,135 records · Page 63Linked to original sources
PubMed1986

Pirenzepine inhibits pancreatic exocrine secretion in the rat.

Pirenzepine is a newly developed anticholinergic drug that reduces gastric acid secretion and is therefore used in Europe and Japan to treat patients with peptic ulcer. The inhibitory effect of pirenzepine on pancreatic exocrine function and its reversibility were studied in the isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, pirenzepine caused a concentration-dependent rightward shift in the dose-response curve for carbamylcholine-stimulated amylase secretion without altering the maximal increase. Addition of 10 microM pirenzepine at the beginning as well as after 10 or 20 min of stimulation with 1 microM carbamylcholine rapidly abolished pancreatic secretions in both the isolated acini and isolated perfused pancreas. The inhibitory effect of pirenzepine was fully reversible in the isolated acini, whereas pirenzepine caused a small residual inhibition on pancreatic exocrine secretion in the isolated perfused pancreas. These results suggest the existence of pirenzepine-sensitive receptors in the pancreatic vagal pathway at a site remote from the acinar cell. The present data indicate that pirenzepine may have an influence on pancreatic exocrine function by inhibiting not only acinar cell cholinergic receptor but also endogenous cholinergic activity of the pancreas when a large dose is given.

Amylases↗
PubMed1986

Action of cholecystokinin analogues on exocrine and endocrine rat pancreas.

In the present study we have examined the abilities of cholecystokinin-(26-33)-amide [CCK-(26-33)-NH2, CCK-8], nonsulfated CCK-(26-33)-NH2 (desulfated CCK-8), CCK-(30-33)-NH2 (CCK-4), CCK-(26-33)-OH (deamidated CCK-8), and succinyl CCK-(27-31)-NH2 (Suc-Des-Asp6,Phe7-CCK-7) to stimulate exocrine pancreatic secretion from both isolated pancreatic acini and isolated perfused pancreas. We have also compared this action with their ability to cause insulin release. The modification of either the N- or C-terminal amino acid residues of CCK-8 decreased in potency, but the magnitude of the stimulation of enzyme secretion caused by a maximally effective peptide concentration was the same. The minimal effective concentration of CCK-8, desulfated CCK-8, and CCK-4 for insulin release from the isolated rat pancreas in the presence of 8.3 mM glucose was the same as that for pancreatic exocrine secretion. In contrast, the concentrations of deamidated CCK-8 and Suc-Des-Asp6,Phe7-CCK-7 required to produce insulin release were 5-10 times higher than those required to cause stimulation of pancreatic enzyme and juice secretion. It is concluded therefore that the N-terminal 4-amino acid residues or the C-terminal 2-amino acid residues of CCK-8 are not essential for biological activity but do contribute to its potency. In addition, the C-terminal 2-amino acid residues and an amide group in the C-terminal phenylalanine residue of CCK-8 appear to be important determinants of the insulin-releasing activity of the CCK peptides.

Amylases↗
PubMed1986

Effect of Bt2cGMP on action of cholecystokinin in isolated perfused rat pancreas.

We have examined the effects of Bt2cGMP on cholecystokinin stimulation of pancreatic exocrine secretion in the isolated perfused rat pancreas. Bt2cGMP produced a concentration-dependent inhibition of the stimulatory effects of cholecystokinin octapeptide (CCK-8, 100 pM) on both pancreatic juice flow and enzyme secretion. Adding 1 mM Bt2cGMP rapidly and completely abolished CCK-8-stimulated pancreatic juice and enzyme secretion. Adding 500 microM Bt2cGMP for 10 min at the termination of 1 nM of CCK-8 infusion caused an immediate and persistent inhibition of the residual response. In contrast, treatment with C-terminal CCK antiserum I had no influence on the residual response. To account for the ability of Bt2cGMP to function as a competitive antagonist of the action of CCK and the ability of the nucleotide to inhibit the residual stimulation caused by CCK, we feel that Bt2cGMP hindered the binding of CCK not only by reducing the association rate constant for hormone binding but also accelerating the dissociation rate.

Amylases↗
PubMed1986

Reno-colic-cutaneous fistula.

A case of reno-colic-cutaneous fistula is presented. Of several diagnostic methods, fistulography combined with computerized tomography was the most useful to locate the precise anatomical site of involvement. Total nephrectomy, resection of the descending colon and excision of the retroperitoneal abscess were successfully performed.

Colonic Diseases↗
PubMed1986

Inferior vena cava thrombus after retroperitoneal lymphadenectomy for testicular tumor.

A rare case of a thrombus in the inferior vena cava (IVC) after retroperitoneal lymphadenectomy for a testicular tumor is reported. A computed tomograph performed after the operation incidentally showed a filling defect in the IVC. However, it was impossible to decide whether the defect was due to an ordinary or a neoplastic thrombus. For this reason, a thrombectomy was performed, and postoperatively it was diagnosed as an ordinary thrombus. The cause of thrombi found only in the IVC is reviewed and the indication for thrombectomy is discussed.

Adult↗
PubMed1986

Urinary tract stone disease in modern Japan. Stone incidence, composition and possible causes in Osaka district.

2,969 stones, obtained from affiliated hospitals as well as the Osaka University Urologic Clinic were analyzed by infrared spectrophotometry. 2,724 of the 2,969 stones were obvious upper urinary tract stones, and the composition of these 2,724 stones is reported. The incidence and possible cause of stones in 750 patients with upper urinary tract calculi, managed in Osaka University Urologic Clinic, are discussed, as well as the recent figures on urinary tract stone disease in Osaka district. These figures are representative of stone disease in Japan.

Adult↗
PubMed1986

Effect of x-ray irradiation on lipid peroxide levels in the rat submandibular gland.

We examined the effect of local x-ray irradiation on the changes in the lipid peroxide level in submandibular gland, liver, and blood plasma. Rats five weeks of age received a single low dose of 3 Gy x-ray irradiation to their neck regions. The lipid peroxide level in the submandibular gland was significantly enhanced at seven days after irradiation, as was the level in the blood plasma at two hours, seven and 14 days after irradiation. The lipid peroxide level in the liver decreased, as compared with levels in the controls. There was a slight tendency for acinar cells of the submandibular gland to show pyknosis and anomalous nuclei within three days after irradiation. These results suggest that radiation injury results in an elevation of the lipid peroxides in the submandibular gland, and an increased level in the blood.

Animals↗
PubMed1986

Dibutyryl guanosine 3',5'-monophosphate inhibits cholecystokinin potentiation of insulin release in the isolated perfused rat pancreas.

(Bu)2cGMP is known to act as a specific competitive inhibitor for gastrin and cholecystokinin (CCK) peptides. We have examined the effects of (Bu)2cGMP on CCK octapeptide (CCK-8) stimulation of insulin release in the isolated perfused pancreas and compared them with those on protein output. Addition of (Bu)2cGMP after a 20-min perfusion with 100 pM CCK-8 resulted in two distinctly different phases of insulin suppression. There was a sharp initial decline in insulin release for 3 min, followed by transient recovery toward the control level for 5 min, and then a small decline until termination of (Bu)2cGMP infusion. (Bu)2cGMP produced a concentration-dependent inhibition of both phases of insulin decrement. (Bu)2cGMP also produced a concentration-dependent inhibition of protein output. Addition of 1 mM (Bu)2cGMP rapidly and completely abolished CCK-8-stimulated protein output. Since CCK is released by meal intake and exogenous CCK stimulates insulin release and augments glucose-induced insulin release, it is possible that endogenous CCK plays an important role in the enteroinsular axis. The present findings of blockade of CCK-8-induced insulin release by selective antagonist of the action of CCK provide evidence for CCK as a mediator in the enteroinsular axis.

Animals↗
PubMed1986

Effect of administration route on the selective lymphatic delivery of cyclosporin A by lipid-surfactant mixed micelles.

The absorption and lymphatic delivery of a new immunosuppressive drug, cyclosporin A (CsA), with the aid of lipid surfactant mixed micelles (MM) system using different administration routes were studied in the thoracic duct cannulated rat model at a dose level of 7 mg/kg. The rectal or intraperitoneal (i.p.) administration of CsA indicated a small amount of CsA in the plasma and in the lymph for 6 h. As oral routes, intrastomach (i.s.) and intraduodenal (i.d.) administration of CsA were performed and high lymph CsA levels were obtained. The i.s. administration of CsA resulted in the highest CsA levels in the lymph, 16 micrograms/ml, about twenty times higher than the rectal or i.p. administration. These results strongly support the usefulness of an oral CsA dosage form for the selective lymphatic delivery of CsA in clinical immunosuppressive therapy by means of a new mixed micelles system.

Administration, Oral↗
PubMed1986

Synergistic anticellular and antiviral activities of human recombinant interferon-gamma and -beta.

The synergism of anticellular and antiviral activities of recombinant human interferon-gamma (ReIFN-gamma) and recombinant human interferon-beta (ReIFN-beta) was examined in vitro using human melanoma SK-MEL-28 cells. Some differences were detected in the kinetics of anticellular activity between both IFNs, namely the inhibitory effect of ReIFN-beta occurred earlier than that of ReIFN-gamma. Significant synergism was detected in the anticellular activity of both IFNs when growth curves and isobolograms were examined. A difference between ReIFN-gamma and ReIFN-beta was also detected in antiviral activity. The antiviral activity of ReIFN-gamma against vesicular stomatitis virus (VSV) was significantly weaker than that of ReIFN-beta, even though both IFNs exhibited almost equivalent antiviral activities against Sindbis virus. However, ReIFN-gamma and ReIFN-beta exhibited synergistic antiviral activities against both VSV and Sindbis virus. The analysis of cell cycle distribution by flow cytometry revealed that there were some differences in the distribution pattern between cells treated with ReIFN-gamma alone, ReIFN-beta alone, or ReIFN-gamma and ReIFN-beta in combination. ReIFN-beta induced a prolongation or accumulation of S phase, whereas the effect of ReIFN-gamma was cycle-nonspecific. The combination of ReIFN-gamma and ReIFN-beta induced a decrease of G1 phase and an increase of G2M phase. These results suggest that ReIFN-gamma and ReIFN-beta used in combination were more effective in inhibiting the growth of human tumor cells and the proliferation of viruses than IFN used individually.

Antineoplastic Agents↗
PubMed1986

Antitumor effect of human recombinant interferon-gamma and -beta against human osteosarcoma transplanted into nude mice.

The antitumor activity of recombinant human interferon-gamma (ReIFN-gamma) and recombinant human interferon-beta (ReIFN-beta) against human osteosarcoma G-292 cells was compared in vitro and in vivo. Both IFNs inhibited the growth of G-292 cells cultured in vitro and transplanted into nude mice in vivo. In in vivo experiment, both IFNs injected i.t. were more effective at inhibiting the growth of G-292 cells than systemic administration such as i.v., i.p. or s.c. In comparing the various routes of systemic administration of both IFNs, i.v. injection was slightly more effective. Both IFNs exhibited more significant growth inhibition when they were administered every day for 10 d, as compared with a single or intermittent administrations, suggesting that the antitumor activity of both IFNs was time-dependent. Significant difference was not detected in the in vivo antitumor activity between both IFNs when they were compared on the basis of their antiviral units. However, the time dependency for antitumor effect of ReIFN-beta was more significant than that of ReIFN-gamma. ReIFN-gamma and ReIFN-beta used in combination exhibited synergistic antitumor activity both in vitro and in vivo, though the in vivo synergism of both IFNs was not so effective as that of in vitro: These results indicate that both ReIFN-gamma and ReIFN-beta are effective at inhibiting the growth of human osteosarcoma in vivo.

Animals↗
PubMed1986

The inactivation of [Met5]-enkephalin by bestatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A and thiorphan-sensitive endopeptidase-24.11 in mouse vas deferens.

The enkephalin-hydrolyzing peptidases in mouse vas deferens were studied and compared with those in guinea pig ileum which had been characterized in the previous study. The present results showed that three distinct peptidases, bestatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A, and thiorphan-sensitive endopeptidase-24.11, played a critical role in the inactivation of enkephalin in mouse vas deferens, being consistent with the previous results obtained with guinea pig ileum. However, the data in both previous and present studies showed that the activity of the bestatin-sensitive aminopeptidase relative to that of either the captopril-sensitive peptidyl dipeptidase A or the thiorphan-sensitive endopeptidase-24.11 in guinea pig ileum was higher than that in mouse vas deferens, while the activity of either peptidyl dipeptidase A or endopeptidase-24.11 relative to that of aminopeptidase in mouse vas deferens was higher than that in guinea-pig ileum. In contrast to these three enzymes, both L-tyrosyl-L-tyrosine-sensitive dipeptidyl aminopeptidase and D-phenylalanine-sensitive carboxypeptidase were suggested not to be involved significantly in the inactivation of enkephalin in mouse vas deferens as well as guinea pig ileum.

Amino Acids, Sulfur↗
PubMed1986

Agonist and antagonist actions of buprenorphine on three types of opioid receptor in isolated preparations.

Both agonist and antagonist actions of buprenorphine on isolated preparations were studied. The Ke (equilibrium dissociation constant) values of both naloxone and Mr 2266 [(-)-2-(3-furylmethyl)-5, 9-diethyl-2'-hydroxy-6,7-benzomorphan] against buprenorphine and the ratio of IC50 (concentration of the drug to produce 50% inhibition of the twitch) value of buprenorphine after to before exposure of mouse vas deferens to beta-FNA (beta-fumarate methyl ester derivatives of naltrexone), an irreversible mu antagonist, suggest that buprenorphine acts as both a mu and kappa agonist on mouse vas deferens. The agonist effect of buprenorphine at relatively high doses on guinea-pig ileum and mouse vas deferens and the negative agonist effect on both rat and rabbit vas deferens indicate that buprenorphine acts as a partial agonist on isolated preparations. The Ke values of buprenorphine show that buprenorphine has about equal antagonist effectiveness against a mu and kappa agonist with approximately five-fold lower effectiveness against a delta agonist. The possible mechanisms for the several characteristic actions of buprenorphine on guinea-pig ileum such as the slow onset of action, the increased magnitude of inhibition after washing the tissue, the negative elimination of the inhibition by either washing the tissue or the naloxone administration, and the negative elimination of the antagonist action by washing the tissue were discussed.

Animals↗
PubMed1986

The relative potency of enkephalins and beta-endorphin in guinea-pig ileum, mouse vas deferens and rat vas deferens after the administration of peptidase inhibitors.

Previous studies have shown that three distinct enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A, and phosphoramidon-sensitive endopeptidase-24.11, played a critical role in the inactivation of enkephalins in isolated preparations. In the present study, therefore, the rank order of the potency of three endogenous opioid peptides, [Met5]-enkephalin, [Leu5]-enkephalin, and beta-endorphin, in three isolated preparations, guinea-pig ileum, mouse vas deferens, and rat vas deferens, was estimated in the presence of the mixture of three peptidase inhibitors, amastatin, captopril, and phosphoramidon. [Met5]-Enkephalin was approximately three-fold more potent than [Leu5]-enkephalin and four-fold more potent than beta-endorphin in guinea-pig ileum in which three opioid peptides were indicated to act on mu-receptors. Additionally, [Met5]-enkephalin was slightly but significantly more potent than [Leu5]-enkephalin and approximately twenty-fold more potent than beta-endorphin at delta-receptor sites in mouse vas deferens. Moreover, [Met5]-enkephalin was approximately three-fold more potent than [Leu5]-enkephalin, but sixty-fold less potent than beta-endorphin in rat vas deferens in which the opioid-receptor type interacting with enkephalins could not be determined. In conclusion, the well-known rank order of the potency of three endogenous opioid peptides was shown to be altered in both guinea-pig ileum and mouse vas deferens but not in rat vas deferens by the pretreatment of the preparations with the mixture of three peptidase inhibitors.

Animals↗
PubMed1986

Effects of peptidase inhibitors on the [Met5]-enkephalin hydrolysis in ileal and striatal preparations of guinea-pig: almost complete protection of degradation by the combination of amastatin, captopril and thiorphan.

The contents of [Met5]-enkephalin and its four hydrolysis products, Tyr, Tyr-Gly, Tyr-Gly-Gly, and Tyr-Gly-Gly-Phe, in the sample obtained after enkephalin was incubated with tissues in either the absence or the presence of the peptidase inhibitor were estimated by high performance liquid chromatography combined with electrochemical detection in order to elucidate the effect of the peptidase inhibitor on enkephalin hydrolysis. Free Tyr was the major degradative product in the absence of the peptidase inhibitor, while the major hydrolysis product was the Tyr-Gly-Gly fragment in the presence of amastatin in both total homogenates and membrane fractions prepared from either the myenteric plexus-longitudinal muscle strip of guinea-pig ileum or the striatum of guinea-pig brain. Additionally, captopril significantly decreased the generation of Tyr-Gly-Gly in the presence of amastatin in both ileal and striatal membrane fractions. Moreover, thiorphan significantly prevented the formation of Tyr-Gly in the presence of both amastatin and captopril in both membrane preparations. Finally, when [Met5]-enkephalin was incubated with either an ileal or a striatal membrane fraction for 60 min at 37 degrees C in the presence of three peptidase inhibitors, amastatin, captopril, and thiorphan, approximately 98 or 94%, respectively, of enkephalin remained intact. The results indicated that [Met5]-enkephalin was almost exclusively hydrolyzed by three distinct enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A, and thiorphan-sensitive endopeptidase-24.11 in both ileal and striatal membrane fractions.

Animals↗
PubMed1986

The enhancing effects of amastatin, phosphoramidon and captopril on the potency of [Met5]-enkephalin in rat vas deferens.

The enkephalin-inactivating enzymes in rat vas deferens were studied by using the relatively specific inhibitor of each enzyme. The results showed that the rat vas deferens, like the other three preparations, guinea-pig ileum, mouse vas deferens and striatal membranes of guinea-pig brain, which had been investigated previously, contained three distinct enkephalin-hydrolyzing peptidases. Additionally, the enkephalin-hydrolyzing aminopeptidase, endopeptidase-24.11 and peptidyl dipeptidase A in rat vas deferens were found to be inhibited maximally with 1 microM of amastatin, 1 microM of phosphoramidon and 1 microM of captopril, respectively. In contrast to these three enzymes, both L-tyrosyl-L-tyrosine-sensitive dipeptidyl aminopeptidase and D-phenylalanine-sensitive carboxypeptidase were suggested not to be involved significantly in the inactivation of exogenously given enkephalin in rat vas deferens. The characteristics of the enkephalin-degradative enzymes in rat vas deferens were discussed in terms of their similarities to and differences from those in the other preparations.

Animals↗
PubMed1986

Regulation of the level of epidermal growth factor by oestrogen in the submandibular gland of female mice.

The concentration of epidermal growth factor (EGF) in the submandibular gland of immature female mice (less than 6 weeks old) was low, ranging from 0.07 to 0.17 pmol (0.4 to 1.0 ng)/mg wet wt, but increasing to 7.61 pmol/mg wet wt by 8 weeks of age. It remained relatively constant up to 24 weeks of age, but thereafter the glandular EGF concentration increased again during the post-reproductive period to reach 62.9 pmol/mg wet wt. In contrast, the glandular EGF content in male mice increased greatly during the first 17 weeks of age to about 310 pmol/mg wet wt, and thereafter remained relatively constant up to 48 weeks of age. Ovariectomy of mature virgin mice markedly increased the glandular concentration of EGF to about 74.4 pmol/mg wet wt 4 weeks after the operation. This increase was suppressed by oestradiol-17 beta administered to ovariectomized mice at a dose of 1 microgram/mouse per day but not by 1 mg progesterone. Histological studies indicated that granular convoluted tubular cells that produced EGF in the submandibular gland were much less abundant in 12-week-old female and in oestrogen-treated ovariectomized mature mice than in 40-week-old female and ovariectomized mature mice. We conclude that oestrogen suppresses the concentration of EGF in the submandibular gland of female mice.

Aging↗