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Biomedical subjects

M Otsuki

Publications and source records attributed to M Otsuki.

At least 253 records · Page 14Linked to original sources
PubMed1987

A case of liver cirrhosis complicated with endotoxemia and disseminated intravascular coagulation: a case report.

A 59-year-old female was admitted to our hospital because of massive ascites and increasing jaundice, suggesting a severe decompensated state of liver cirrhosis. On the third hospital day, she was diagnosed as disseminated intravascular coagulation (DIC) from a coagulofibrinolytic study and developed renal failure. Continuous drip infusion of gabexate mesilate, a synthetic inhibitor of serine-protease, was found to be successful in managing DIC, followed by the restoration of renal function. During the clinical course, blood endotoxin, assayed by the chromogenic method, was initially 11 pg/ml and increased, in accordance with the elevation of serum FDP, to a level of 110 pg/ml when renal failure occurred. A proportional relationship was observed between changes in blood endotoxin and serum FDP throughout the course. This finding may be an important clue in studying the mechanism of DIC and non-septic endotoxemia both developing in liver cirrhosis.

Disseminated Intravascular Coagulation↗
PubMed1987

An improved method for observing the cytoskeleton around the bile canaliculi of rat hepatocytes.

In order to know more about the cytoskeletal structure around the bile canaliculi of hepatocytes, we used the following procedure. Liver specimens were passed through an 18-, a 21- and then a 23-gauge needle, by which they turned into cylindrical or oval blocks of 0.4 mm in diameter. Because of their small size, the cytosolic ground substances of every hepatocyte were washed out clearly after subsequent treatment with the solution containing 0.5% Triton X-100 and 0.5 mg/ml saponin for 15 min. This short-term extraction preserved both the cytoskeleton and the plasma membrane of the hypatocyte quite well, and we could observe the crossbridge filaments connecting between a core bundle of microfilaments and plasma membrane of the microvilli of the bile canaliculi.

Animals↗
PubMed1986

Effect of CS-514, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on lipoprotein and apolipoprotein in plasma of hypercholesterolemic diabetics.

CS-514, one of the derivatives of ML-236B which is an inhibitor of endogenous cholesterol synthesis, has been previously shown to effectively reduce low density lipoprotein (LDL) cholesterol in dogs, rabbits and humans. We determined the effect of CS-514 on glucose, lipid, lipoprotein and apolipoprotein (apo) levels in plasma of 8 hypercholesterolemic diabetics (2 males). Total and LDL cholesterol and apo B levels were significantly decreased (P less than 0.005) 3 months after CS-514 treatment. High density lipoprotein (HDL) cholesterol was increased (P less than 0.05). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) did not change throughout the observation period. No clinically serious adverse effects were experienced by the patients. We conclude that CS-514 can be a useful drug in the treatment of hypercholesterolemic diabetics and is remarkably free of any evidence of toxicity or unwanted side effects even in diabetics.

Apolipoproteins↗
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

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

Stability of endotoxin detected in human plasma against endotoxin-inactivating factor (EIF): quantitative analysis of EIF using chromogenic endotoxin assay.

Using a quantitative blood endotoxin assay utilizing chromogenic substrate coupled with perchloric acid pretreatment (PCA-LCT), we showed the presence of endotoxin-inactivating factor (EIF) in human plasma in vitro. EIF activity inactivated added endotoxin to about 10(-4) of the initial level within 20 min, followed by a stable phase where the residual endotoxin became resistant to EIF and was not further inactivated. The residual endotoxin may represent the endotoxin in patient plasma which is also EIF resistant. We postulate that endotoxin, upon entering the blood, is rapidly inactivated by chemical modification of its active site, lipid A, through EIF. Subsequently, inactivated endotoxin, mainly consisting of polysaccharide, is gradually removed from circulation by endocytosis in the reticuloendothelial system.

Chromogenic Compounds↗
PubMed1986

[In vitro susceptibility of bacterial isolates from patients with respiratory tract infections to beta-lactam antibiotics].

In vitro susceptibilities of bacterial pathogens to beta-lactam antibiotics were determined. Bacterial pathogens examined included various isolates from the patients of respiratory tract infections at the hospitals of Kyoto-Shiga area in 1981 and 1983. Major organisms isolated from clinical specimens were Haemophilus spp., Klebsiella spp., Pseudomonas spp., S. aureus and Streptococcus spp. An increase in the isolation frequency of P. aeruginosa, a decrease in the isolation frequency of H. influenzae and no change in the isolation frequency of the other organisms were observed between the years 1981 and 1983. Data from susceptibility tests of clinical isolates confirmed that cefazolin (CEZ) and cefotiam (CTM) showed good antibacterial activity against S. aureus and cefmenoxime (CMX) was highly effective on Streptococcus spp., but that the susceptibilities of both organisms to CEZ, CTM, and cefmetazole (CMZ) in 1983 were lower than in 1981. Although CMX also showed good antibacterial activity against Klebsiella spp., there were no changes in the effectiveness of CTM, CMZ, and CEZ between the years 1981 and 1983. The in vitro antibacterial activities of CMX and cefoperazone against Haemophilus spp. were superior to those of the other beta-lactams tested, but there was a decline in the efficacy for CEZ. Although cefsulodin and piperacillin were highly active against Pseudomonas spp., declines in their effectiveness was observed between the years 1981 and 1983.

Adolescent↗
PubMed1986

[In vitro susceptibility, of bacterial isolates from patients with respiratory tract infections, to beta-lactam antibiotics II].

In vitro susceptibilities of bacterial pathogens to beta-lactam antibiotics were determined. Bacterial pathogens examined included various isolates from patients of respiratory tract infections at hospitals of Kyoto-Shiga area in 1984. Major organisms isolated from clinical specimens were Pseudomonas spp., Klebsiella spp., Haemophilus spp., Staphylococcus aureus and Streptococcus spp. An increase in the isolation frequency of Pseudomonas spp., a decrease in the isolation frequency of S. aureus, and no change in the isolation frequency of other organisms were observed between the years 1981, 1983 and 1984. Data from susceptibility tests of clinical isolates confirmed that cefazolin (CEZ), cefamandole and cefotiam (CTM) showed good antibacterial activity against S. aureus and cefmenoxime (CMX) was highly active against Streptococcus spp., but their susceptibilities to CEZ in 1984 were lower than in 1983. Susceptibilities of Klebsiella spp. to CMX, cefbuperazone, latamoxef, CTM, cefoperazone (CPZ) were better than those to other beta-lactam antibiotics tested, but there was a decline in the susceptibility to CEZ, cefmetazole and CTM. Further, CMX, CPZ and LMOX also showed good antibacterial activity against Haemophilus spp. Although gentamicin, cefsulodin, cefpiramide and piperacillin were highly active against Pseudomonas spp., resistant organisms were present for all the beta-lactam antibiotics tested.

Anti-Bacterial Agents↗