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Biomedical subjects

S Tani

Publications and source records attributed to S Tani.

At least 145 records · Page 8Linked to original sources

Comparative studies of two types of acid proteases from rat gastric mucosa and spleen.

Two types of acid proteases, cathepsin D and cathepsin E-like enzyme, from rat gastric mucosa and spleen were compared in their biochemical and immunochemical properties. The enzymes were partially purified by employing the same chromatographic procedures and they showed a single proteolytically active band in polyacrylamide gel electrophoresis. Two low molecular weight enzymes, cathepsins D, from both tissues showed the same molecular weight and the same sensitivities to various inhibitors, but slightly different electrophoretic mobilities. The rabbit antiserum raised against gastric mucosa cathepsin D precipitated both enzymes. On the other hand, high molecular weight enzymes, gastric mucosa cathepsin D-like acid proteinase and spleen cathepsin E-like acid proteinase, were similar to each other as judged by their chromatographic profiles, electrophoretic mobilities, and high stabilities in urea solution. Furthermore, the antiserum specific to gastric mucosa cathepsin D-like acid proteinase inhibited both enzyme activities in a similar manner. However, the antiserum specific to one type of enzyme did not react with the other type. These results indicate that: gastric mucosa cathepsin D is immunologically identical with spleen cathepsin D; gastric mucosa cathepsin D-like acid proteinase has biochemical and immunological properties quite similar to spleen cathepsin E-like enzyme; these two types of acid proteases are quite different proteins existing in the individual tissues.

Animals↗

Actions of neuromedin-B and neuromedin-C on amylase release from isolated rat pancreatic acini.

Neuromedin-B and neuromedin-C are novel decapeptides which have recently been isolated from porcine spinal cord and canine intestinal muscle, and show striking sequence homology with gastrin-releasing peptide (GRP-27) at the carboxyl-terminal region. The effects of synthetic neuromedin-B and neuromedin-C on exocrine pancreatic function were examined using isolated rat pancreatic acini. Neuromedin-B and neuromedin-C were able to cause full stimulation of amylase release. The relative efficacy of neuromedin-B and neuromedin-C was the same as that of GRP-27. Neuromedin-C was about twofold more potent, whereas, neuromedin-B was about 10-fold less potent than GRP-27. Both neuromedin-B and neuromedin-C potentiated the stimulation of amylase release caused by vasoactive intestinal peptide, secretin, or forskolin. Potentiation of amylase secretion did not occur with neuromedin-B or neuromedin-C plus cholecystokinin (CCK), carbamylcholine, or Ca2+ ionophore A23187. The effects of neuromedin-B and neuromedin-C on enzyme secretion were inhibited neither by dibutyryl cyclic GMP, nor atropine. The present study suggests that neuromedin-B and neuromedin-C act on different receptors than CCK and cholinergic agents, but appear to activate a common intracellular mechanism.

Amylases↗

Effects of neuromedin B and neuromedin C on exocrine and endocrine rat pancreas.

Neuromedin B and neuromedin C are novel decapeptides that have recently been isolated from porcine spinal cord and canine intestinal mucosa and show striking sequence homology with bombesin and gastrin-releasing peptide (GRP-27) at the carboxyl-terminal region. The effects of synthetic neuromedin B and C on exocrine pancreatic function and insulin release have been compared with bombesin and GRP-27 in isolated pancreatic acini and isolated perfused pancreas in rat. Neuromedin B and C as well as bombesin and GRP-27 were able to cause stimulation of amylase release. The relative efficacy of neuromedin B, C, bombesin, and GRP-27 was the same as that of cholecystokinin octapeptide (CCK-8). Bombesin and GRP-27 were equipotent, and both were approximately 15-fold less potent than CCK-8. Neuromedin C was approximately 2-fold more potent, whereas neuromedin B as approximately 10-fold less potent than bombesin and GRP-27. All of these peptides stimulated insulin release that was limited to the first 3 min of a 20-min perfusion. However, GRP-27 and its related peptides were weak stimulants of insulin release compared with their abilities to stimulate exocrine pancreatic secretion. Bombesin and neuromedin B id not stimulate insulin release at doses stimulating pancreatic exocrine secretion. Neuromedin B was also approximately 10-fold less potent than neuromedin C, bombesin, and GRP-27 in eliciting insulin secretion. Because bombesin-like immunoreactivity is found to be present in nerves in the pancreas, neuromedin B and C may be neurotransmitters or neuromodulators and exert a direct local neurocrine action on enzyme secretion by acinar cells and insulin secretion by the islets.

Amylases↗

Alteration in gastric mucosal acid protease activity induced by necrotizing agents and prevention by prostaglandin E2.

Tissue levels of two gastric mucosal acid proteases, pepsinogen and cathepsin D-like acid proteinase, were determined in rat gastric mucosa damaged by various necrotizing agents and the protective effects of prostaglandins against these biological alterations were investigated. Gastric mucosal damage by each necrotizing agent used was associated with a marked decrease in tissue level of cathepsin D-like acid proteinase. Particularly, ethanol ingestion caused its significant reduction parallel to the production of gastric lesions in a time-dependent manner. On the other hand, mucosal pepsinogen level increased markedly only in ethanol-damaged gastric mucosa, indicating that this change was mediated by a different mechanism from that for cathepsin D-like enzyme. In rats pretreated with prostaglandin E2 and prostaglandin inducers before ethanol administration, these biological alterations of two enzymes were effectively prevented as were gastric lesions. However, ethanol ingestion caused these changes to occur to the same degree in both the necrotic and non-necrotic areas of glandular mucosa. It was considered that cathepsin D-like acid proteinase was released from damaged gastric mucosa through a direct action on cellular membrane different from vasoconstrictor and platelet aggregating actions mediated by arachidonic acid metabolites.

Animals↗

Extensibility of the lumbar and sacral cord. Pathophysiology of the tethered spinal cord in cats.

Tethered spinal cord, or tethered cord syndrome, describes a disorder manifested by progressive motor and sensory deficit in the legs and by incontinence. Tethered cord syndrome occurs when the elongated spinal cord is anchored by a thick filum terminale or other pathological structures. The underlying mechanism is impairment of oxidative metabolism in the lumbosacral cord. The authors studied the extensibility of various parts of lumbar, sacral, and coccygeal segments in experimental animals and correlated this with the oxidative metabolism in these segments. The filum terminale possesses far greater extensibility than any spinal cord segments and functions as a buffer in preventing the cord from overstretching. The lumbar, sacral, and coccygeal segments elongate under traction only below the attachment of the lowest pair of dentate ligaments. The lower the cord segment, the greater the percentage of elongation in spite of limited elasticity of the cord tissue; this greater percentage of elongation of the spinal cord correlates with increasing impairment of the oxidative metabolism and more severe neurological deficit. These findings explain such symptoms and signs as motor and sensory deficits in the legs associated with the human tethered cord syndrome, and correspond with the high clinical incidence of incontinence. The lower spinal cord segments elongated promptly within 3 seconds after the start of traction. This implies that repeated acute hyperextension and hyperflexion, as occurs in humans, may accentuate oxidative metabolic changes that have already been caused by chronic cord tethering. The authors conclude that the elongation of the spinal cord under traction parallels the degree of metabolic dysfunction.

Animals↗

Lymphographic changes in young dogs after transplantation with adult worms of Dirofilaria immitis into the abdominal cavity.

Serial lymphographic studies were made in 4 dogs transplanted with adult worms of Dirofilaria immitis. Several changes of the lymphatic systems of the treated dogs such as dilatation, narrowing, tortuosity, backflow, collateral flow, leakage and lymphorrhea of lymphatics, as well as enlargement and filling defect of lymphnodes were observed at first 2 months after transplantation, comparing with the lymphograms before transplantation. Lymphographies were repeated further 4 and 7 months after transplantation. In our previous studies, the mechanism of chyluria due to human filariasis was not sufficiently explained beyond the speculation of the mechanical obstruction of lymphatic vessels by worm bodies. In the present studies, varied abnormal changes, especially back and collateral flow of the lymph vessels of popliteal and inguinal regions, could be produced in lymphatic systems in dogs by transplantation with adult worms of Dirofilaria immitis into peritoneal cavity. This fact suggests that a mechanism of filarial chyluria is due to systemic responses and changes of the lymphatics by substance of the body of filarial worms.

Animals↗

Antitumor agents. 78. Inhibition of human DNA topoisomerase II by podophyllotoxin and alpha-peltatin analogues.

It has been reported that the action of etoposide (VP-16) (14) as an antitumor agent is mediated through its interaction with DNA topoisomerase II which results in DNA breakage inside the cell. In order to understand the mechanism of action as well as structure-activity relationships of 14, several novel, synthetic and some naturally occurring analogues related to podophyllotoxin were examined for inhibition of the DNA topoisomerase II activity. Compound 2 exhibited enhanced activity and compound 5 slightly diminished activity relative to 14. A 4 beta-substituted ether at the C ring and O-demethylation at the E ring appear to enhance activity.

Antineoplastic Agents, Phytogenic↗

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↗