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Biomedical subjects

K Kondoh

Publications and source records attributed to K Kondoh.

At least 19 recordsLinked to original sources
PubMed1992

Saposin-C from bovine spleen; complete amino acid sequence and relation between the structure and its biological activity.

Saposin-C, a small acidic glycoprotein that can activate glucosylceramide-beta-glucosidase, has been isolated from bovine spleen. The complete amino acid sequence of bovine saposin-C was determined by Edman degradation of the purified protein and its fragmented peptides. It contains 80 amino acids, one carbohydrate chain attached to a single asparagine residue and six cysteine residues in oxidized form. The sequence of bovine saposin-C is 76 and 65% identical with the sequences of saposin-C from human spleen and guinea pig liver, respectively. Hydropathy profiles of the sequence of saposin-C from three species were similar despite the significant residue substitutions. Bovine saposin-C had a stronger effect in stimulating bovine beta-glucosidase compared to human saposin-C. However, the effect of human saposin-C in stimulating human enzyme was stronger than that of bovine saposin-C. The region around residue 35, which is next to the extremely hydrophilic region, seems to be important to produce an interaction with the enzyme.

Amino Acid Sequence↗
PubMed1992

Polyoxyethylene-modified superoxide dismutase reduces side effects of adriamycin and mitomycin C.

Polyoxyethylene-modified superoxide dismutase (SOD-POE) is a newly developed long-acting superoxide dismutase. Adriamycin (ADR) and mitomycin C (MMC) generate superoxide, which contributes to their cytocidal effects or side effects. We examined whether SOD-POE could prevent the side effects induced by superoxide generated by antitumor agents, and the following results were obtained. SOD-POE did not influence the antitumor effects of ADR and MMC either in vitro or in vivo, but prevented the toxic death of BALB/c, nu/nu male mice caused by overdoses of ADR or MMC. As for its effective sites, SOD-POE prevented a decrease in the specific activity of rotenone-sensitive NADH-ubiquinone oxido-reductase (complex I) in heart muscle mitochondrial respiratory chain function in BALB/c male mice administered 10 mg/kg ADR, and prevented damage to the sarcoplasmic reticulum and mitochondria of mouse heart muscle by ADR as observed by electron microscopy. Furthermore, SOD-POE prevented bone marrow suppression induced by MMC in Donryu rats. The above results suggest that combination chemotherapy with SOD-POE would make it possible to increase the maximum permissible doses of antitumor agents, improving the efficacy of these agents.

Animals↗
PubMed1992

Distribution of free methylarginines in rat tissues and in the bovine brain.

A sensitive and specific method for determining three forms of methylarginine, i.e., NG-monomethylarginine, NG,NG-dimethylarginine, and NG,N'G-dimethylarginine, in mammalian tissues was developed. After partial purification by ion-exchange chromatography, the methylarginines were derivatized to phenylthiocarbamyl compounds and quantitatively determined using HPLC with a reverse-phase C18 column. In rat organs, the highest concentrations of methylarginines were observed in the spleen. In rat brain, cerebellum and olfactory bulb contained large amounts of NG-monomethylarginine and NG,NG-dimethylarginine. A detailed study of the distribution of methylarginines in the bovine brain was also made, and the concentration of NG,N'G-dimethylarginine was almost the same in all regions. The cerebellar gray matter, hippocampus, and hypothalamus contained large amounts of methylarginines. The distribution of methylarginines seems to parallel the distribution of nitric oxide synthase, which is known to be inhibited by NG-monomethylarginine. This may indicate that methylarginines play some role in controlling nitric oxide synthase activity.

Animals↗
PubMed1992

Effects of alternately aligned static micromagnetic fields on intravascular endothelial lining.

Effect of alternately aligned static micromagnetic fields on intravascular endothelial linings were investigated in 32 common carotid arteries of mongrel dogs. Endothelia of bilateral carotid arteries were mechanically denuded 5 cm in length, and as a general rule, 1 denuded artery was wrapped by a 1- or 5-cm-long film of alternately aligned static micromagnetic fields with 250 gauss/cm2 and the artery on other side (control) was not wrapped. The arteries were excised at weeks 1, 2, 3, 4, 5, 6, and 8 after endothelial denudation in order to examine the intraluminal surfaces of the distal, intermediate, and proximal portions of the specimen by light and scanning electron microscopy. Histopathologically, all the distal and proximal portions in each group were well lined with endothelium. There was, however, a significant difference between the experimental and control groups in the endothelial regeneration of the intermediate portion. Endothelial coverage of the serial specimens of the experimental group was found to occur earlier than that of the control group. Alternately aligned static micromagnetic fields accelerated the intravascular endothelial linings.

Animals↗
PubMed1992

DNA polymerase alpha, beta, and gamma activities in human lymphocytes stimulated by Tora-mame (Phaseolus vulgaris) lectin.

We measured the levels of the DNA polymerases alpha, beta, and gamma in human peripheral lymphocyte cells stimulated with Tora-mame lectin (TM-lectin) and the induction patterns were compared to those with other plant lectins, i.e., phytohemagglutinin (PHA) and pokeweed mitogen (PWM). The maximum activity of DNA polymerase alpha in lymphocytes was achieved at the concentration of 10 micrograms/ml with TM lectin and the dose response curve of TM lectin showed a sharp peak in contrast to that of PWM. During prolonged stimulation for 10 days, the time course of DNA polymerase alpha induction was different among these three lectins. A peak of alpha-enzyme was correlated with maximal incorporation of [3H]thymidine and was observed on the fourth day with TM lectin, on the third day with PHA, and sixth day with PWM. DNA polymerase beta in lymphocytes was also activated by the addition of these proteins. Two different peaks were observed during a 10-day period with every lectin, and TM lectin was most potent stimulator among them. The activity of DNA polymerase gamma in lymphocytes was at a very low but detectable level which increased slightly in response to TM lectin treatment. Although some variability of gamma-enzyme activity was observed after the seventh day, the pattern in the course of 7 days was similar among the lectins.

Cells, Cultured↗
PubMed1992

[Coronary artery bypass utilizing vein grafts: why didn't we use an arterial graft?].

Internal thoracic artery (ITA) grafts for coronary artery bypass grafting (CABG) are superior to SVG in the long-term patency and survival. In spite of our effort to utilize ITA whenever possible, we still have some cases which have to receive only vein grafts. Among the consecutive 201 patients undergoing CABG in the past three years, 32 patients (16%) received only vein grafts. We compared these patients (SVG group) with those who received ITA grafts (ITA group). The SVG group consisted of all emergency cases and many cases with single and double vessel disease. In the SVG group, perioperative use of IABP was more frequent and operative mortality was higher, although the number of grafts was fewer (2.66 vs 3.61) and aortic cross clamping time was shorter in this group. Main reasons for selecting only vein grafts were emergency surgery, inadvertent injury of ITA, inadequate ITA free flow etc. Technical refinement in the preparation of ITA is important to make possible wider application of arterial grafts for CABG.

Aged↗
PubMed1992

[The results and problems of reoperation for coronary artery disease].

In six hundred and six consecutive patients undergoing coronary artery bypass grafting (CABG) within the past 17 years (May 1974 to March 1991), repeated CABG were performed on 10 patients (1.65%). The main reasons for repeated CABG were graft failure (GF) in 8, progression of native disease (NP) in 5 and incomplete revascularization (IR) in 3 patients. The incidence of GF was high either within a half year or around 5 years after CABG. Although all patients survived from reoperation, four patients continued to have mild angina pectoris. When the recurrence of angina is noted after CABG, coronary arteriography and if necessary PTCA should be done as soon as possible. If a second surgery is inevitable, maximum utilization of arterial graft and accomplishment of complete revascularization are emphasized.

Aged↗
PubMed1992

[A case of coronary artery bypass for bilateral coronary ostial stenosis in aortitis syndrome with occlusion of bilateral subclavian arteries].

A 52-year-old female with bilateral coronary ostial stenosis in aortitis syndrome underwent CABG. Vein grafts were used instead of arterial grafts, because of the occlusion of bilateral subclavian arteries. Proximal anastomosis of the grafts was performed after oval stomas larger than usual were created on the aortic wall to prevent late graft occlusion due to intimal proliferation of the aorta. On postoperative CAG, all grafts to RCA, LAD and Cx were patent. The patient left the hospital 3 weeks after surgery. We believe that CABG is preferable to the transaortic endarterectomy in the surgical treatment for coronary ostial stenosis associated with aortitis syndrome, because of the prevalence of technical difficulty and postoperative morbidity in the latter.

Aortic Arch Syndromes↗
PubMed1991

Isolation and characterization of prosaposin from human milk.

Prosaposin is the precursor protein for saposins, which are small lysosomal proteins required for the hydrolysis of sphingolipids by specific lysosomal hydrolases. Prosaposin, in addition to generating the saposins in the lysosomes, also exists as an unprocessed approximately 70-kDa protein in many tissues and secretory fluids. In this study, we isolated prosaposin from human milk. Milk was fractioned by ammonium sulfate precipitation, then chromatographed with DEAE-Sephacel and G-3000 SW gel permeation-HPLC. A fraction containing prosaposin was finally purified with the anti-saposin C IgG attached affinity column. The protein staining of the purified preparation on SDS-PAGE and the Western blotting showed a single band. The sequence of the initial 10 amino acids from N-terminus of the purified protein was identical to the sequence of prosaposin deduced from cDNA. Although prosaposin itself showed beta-glucosidase activator activity at a slight degree, the activity increased much after trypsin treatment. Western blotting of the trypsin-treated sample confirmed the formation of small saposin-like bands from prosaposin by the action of trypsin.

Amino Acid Sequence↗
PubMed1991

Secretion of sphingolipid hydrolase activator precursor, prosaposin.

Sphingolipid hydrolases are activated by activator proteins or saposins. The precursor protein has been expected from the studies on the cDNA for saposins. Here we demonstrate that prosaposin occurs in various kinds of human secretory fluids such as cerebrospinal fluid, semen, milk, pancreatic juice, and bile. However, mature type saposins were not detected in these fluids. In human milk the amount of prosaposin changed during the lactating period; it became high in concentration within a few days after delivery, decreased during the transitional milk lactating stage, and then increased again toward the mature milk lactating stage. Prosaposin was released from human platelets in response to stimulation by thrombin, but mature saposins were not. From the time course of the release of prosaposin induced by thrombin and from the fact that weak platelet agonists, ADP, epinephrine, and collagen, did not cause the release of prosaposin, prosaposin secretion from platelets seemed to be from lysosome like granules. We postulate that some prosaposin works as a precursor for saposins in the lysosomes and the other serves as an extracellular protein with other specific roles.

Adenosine Diphosphate↗
PubMed1991

[Effect of AS-2646, a novel antiulcer agent on gastric mucosal defensive factors in rats].

The effects of AS-2646 on the acute gastric mucosal lesions induced by various noxious agents and the gastric mucosal defensive factors were studied in rats, and the following results were obtained: 1) AS-2646 (5-100 mg/kg, p.o.) dose-dependently inhibited the formation of the mucosal lesions induced by ethanol, ethanol-HCl, taurocholate-HCl and serotonin, and its anti-lesion spectrum was the widest among the compounds (cimetidine, pirenzepine, sulpiride and prostaglandin E1) examined here. 2) AS-2646 (5-10 mg/kg, p.o.) not only improved the changes of gastric mucosal hemodynamics induced by the blood removal and/or the reserpine treatment, but also inhibited the mucosal lesions induced by them. 3) AS-2646 (2-20 mg/kg, p.o.) antagonized the decrease in the surface gastric mucus and mucosal hexosamine contents induced by stress and/or aspirin. 4) AS-2646 (2-20 mg/kg, p.o.) caused no significant effect on the gastric mucosal prostaglandin E2 levels. 5) AS-2646 inhibited Campylobacter pylori in vitro. These results indicate that AS-2646 may be useful as a novel antiulcer drug with the defensive factor-potentiating and anti-Campylobacter pylori effects.

Animals↗
PubMed1991

[Hyper-thermo chemotherapy of esophageal cancer with thermosensitive liposome, TAC-1043].

Antitumor activity of the thermosensitive liposome, TAC-1043, was examined. The TAC-1043, produced by Takeda Chemical Industries, Ltd., contained entrapped cisplatin in a large unilamellar vesicle (LUV). LUV is composed of dipalmitoylphosphatidyl choline (DPPC) and distearoylphosphatidyl choline (DSPC) in the ratio of 9:1. The in vitro sensitivity of TAC-1043 was examined by SDI assay with MTT, using human esophageal cancer cell lines (TE-2, KY). TAC-1043 was effective at the concentration of 10 micrograms/ml, 41 degrees C and 43 degrees C. The in vivo effect of TAC-1043 together with hyperthermia was examined using mouse tumor MM 48. TAC-1043 combined with hyperthermia significantly suppressed the tumor proliferation.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Further studies on D-3-aminoisobutyrate-pyruvate aminotransferase.

D-3-Aminoisobutyrate-pyruvate aminotransferase (EC 2.6.1.40, D-BAIB aminotransferase) participates in the metabolism of thymine. Recently we purified this enzyme from rat liver. We have studied D-BAIB aminotransferase further to clarify its physiological function. Among our findings were the following. (1) The enzyme activity was widely distributed in the organs of guinea pigs and rats. The kidney, liver, and lung showed high specific activities. (2) Using the livers of six vertebrates, differences between species were studied. Activity was detected in all species, the human liver showing the lowest activity among them. (3) Developmental study using rat liver showed that the activity was low at birth, increased sharply thereafter for 10 days, and then subsequently declined to the adult level. (4) Intraperitoneal injection of BAIB and beta-alanine in rats was performed to determine whether they induce activity of this aminotransferase. Only BAIB increased the activity of the aminotransferase in the liver significantly. (5) Subcellular distribution study of this aminotransferase in rat liver revealed that it is a mitochondrial enzyme.

Aging↗
PubMed1990

Effect of gastric mucus on the uptake of the carcinogen MNNG by gastric mucosal DNA.

In prostaglandin E2 (PGE2)-, pirenzepine-, and indomethacin-administered rats, the incorporation of N-[methyl-3H]-N'-nitro-N-nitrosoguanidine ([methyl-3H]MNNG) into gastric mucosal DNA was measured quantitatively by liquid scintillation counting after intragastric instillation of [methyl-3H]MNNG. The amount of incorporation was 25.4 +/- 5.9 pmol/mg DNA in control rats, 11.7 +/- 3.8 pmol/mg DNA in PGE2-administered rats, 6.2 +/- 5.6 pmol/mg DNA in pirenzepine-administered rats, and 42.9 +/- 14.4 pmol/mg DNA in indomethacin-administered rats. PGE2 and pirenzepine significantly decreased the incorporation as compared with the control group. In contrast, indomethacin increased the incorporation. In addition, gastric mucosa of these drug-treated rats was studied histochemically. PGE2 and pirenzepine increased secretion of gastric mucus whereas indomethacin decreased it. It is possible that gastric mucus has a protective effect not only against ulcerogenic agents but also against carcinogens. It is considered that gastric mucus plays an important role in the defense mechanism against carcinogenesis.

Animals↗
PubMed1990

[A case of hepatocellular carcinoma treated by intrahepatic arterial administration of anticancer agents: serial determination of the concentration of the chemotherapeutic agents in serum and dialysate during hemodialysis].

The concentration of adriamycin (ADR) and mitomycin C (MMC) were measured in serum and dialysate in a patient with hepatocellular carcinoma complicating chronic renal failure. ADR at a dose of 20 mg and MMC at 10 mg were administered through the hepatic artery or peripheral vein during hemodialysis. ADR and MMC became undetectable after 24 hours and 2 hours, respectively. On the other hand, while MMC was detected in dialysate, but ADR was not. Consequently, it was speculated smaller molecular weight of MMC (334.34) than that of ADR (579.99) might be responsible for the appearance of MMC in dialysate. These results suggest that hemodialysis may be effective in reducing side effects of certain anticancer agents. Serum concentration of the anticancer agents injected through hepatic artery was similar to that injected intravenously.

Adult↗
PubMed1990

[Contractile properties of coronary artery bypass conduit--comparison between saphenous vein and internal mammary artery].

This study was designed to examine the response of coronary artery bypass conduit to serotonin, phenylephrine, and ergonovine as provocation agents of vasoconstriction. Saphenous veins (SV) and internal mammary arteries (IMA) were obtained during coronary artery bypass grafting (CABG), and their contractile properties were measured using isometric contraction recording apparatus. Both SV and IMA showed sigmoid contraction curves indicating dose dependence to ergonovine, serotonin, and phenylephrine. The concentration-response relations for phenylephrine showed a similar curve in both SV and IMA, however, those for ergonovine and serotonin showed a leftward shift in SV compared with IMA. Half maximum effective dose for ergonovine and serotonin were less in SV than IMA. From these results, it was suggested that "perioperative spasm" during CABG might occur not only in coronary arteries but also in the graft conduit itself. Graft spasm might be a possible mechanism for occlusion of the bypass graft. In conclusion, greater hyperreactivity of SV compared with IMA in response to ergonovine and serotonin was suggested, so it is concluded that, from this point of view, IMA is more suitable for use in CABG.

Coronary Artery Bypass↗
PubMed1989

Sphingolipid hydrolase activator proteins and their precursors.

Activator proteins for sphingolipid hydrolases (saposins) are small acidic, heat-stable glycoproteins that stimulate the hydrolysis of sphingolipids by lysosomal enzymes. The molecular mass of each stimulator is about 10 kDa, but glycosylated forms of higher mass exist too. The distribution and developmental changes in two saposins and their precursor proteins were studied with the aid of monospecific antibodies against saposin-B and saposin-C. They show a wide distribution in rat organs and forms intermediate between saposin and prosaposin (the precursor protein containing four different saposin units) could be seen. The amount of saposin and the degree of processing from prosaposin are quite different in different tissues. The saposins are the dominant forms in spleen, lung, liver, and kidney, while skeletal muscle, heart, and brain contain mainly precursor forms. In human blood, leukocytes contain mainly saposin, while plasma contains mainly precursor forms and platelets show many forms. Their subcellular distribution was studied using rat liver. The saposins of approximately 20 kDa are dominant in the light mitochondrial, mitochondrial, and microsomal fractions, following the distribution of the activity of a lysosomal marker enzyme. The nuclear fraction exhibits bands corresponding to non-glycosylated saposin. The soluble fraction contained much precursor forms. A developmental study of rat brain showed that the concentration of saposin precursors increased with age.

Animals↗