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Biomedical subjects

S Kudo

Publications and source records attributed to S Kudo.

At least 73 records · Page 4Linked to original sources

Effect of decaglycerol monooleate on phagocytosis and respiratory burst activity of human neutrophils: an in vitro study.

Decaglycerol monooleate (DGMO), a type of polyglycerol esters of fatty acids (PGEF), was evaluated for its in vitro effect on phagocytosis and respiratory burst activity of isolated human neutrophils using flow cytometric assay. Opsonized zymosan particles labelled with FITC (FITC-OZ) were employed as an indicator of phagocytosis. Fluorescence of FITC-OZ attached on to the surface of neutrophils was quenched by addition of trypan blue solution. After 10 minutes of incubation with DGMO up to a concentration of 10 mg/ml, neutrophil phagocytosis was not affected markedly. At the same time, the DGMO emulsion left little influence on complement receptor type three (CR3) that is associated with phagocytosis. On the other hand, oxidation of hydroethidine, which was used as an indicator of intracellular generation of reactive oxygen species (mainly for superoxide anion), was significantly inhibited by DGMO over 1 mg/ml. However, this phenomenon was not seen in DGMO-treated neutrophils when DGMO was removed after incubation. The present data suggest that DGMO does not affect phagocytosis of human neutrophils but down-regulates respiratory burst activity.

Adult↗

Enzymes responsible for the bactericidal effect in extracts of vitelline and fertilisation envelopes of rainbow trout eggs.

Extracts from both the vitelline envelope (VE) and fertilisation envelopes (FE) of rainbow trout eggs have the ability to exert a bactericidal effect on Gram-positive and -negative bacteria. The effect may be due to the presence of phospholipase D (PLD), lysozyme, proteinase and DNases, as the extracts contain these enzyme activities. The intensity of chorionic PLD and lysozyme activities in the VE extract was maintained in the FE without any alteration in activity even after transformation in the course of the cortical reaction, as components of a fundamental architecture of the envelope. Both extracts also contain different types of proteinase activities. Treatment with VE or FE extract seriously damaged the outer membrane of Gram-negative bacteria and the plasma membrane of Gram-positive and -negative bacteria at the ultrastructural level. Chorionic DNases probably degrade DNA of bacterial cells killed by virtue of the action of PLD and/or lysozyme and contribute to the transmigration of nucleosides and/or nucleotides produced by degrading bacterial DNA after degradation of bacterial components by the actions of the chorionic PLD, lysozyme and proteinase. These results suggest that the bactericidal process manifested by the VE or FE extract may start with the action of PLD and/or lysozyme against bacteria and be completed by subsequent degradation of constitutive proteins and DNA by the action of proteinases and DNases, respectively. Thus the VE and FE are able to protect the egg itself and the embryo, respectively, from bacterial infection in the internal or external environments.

Animals↗

A new method for assaying adhesion of cancer cells to the greater omentum and its application for evaluating anti-adhesion activities of chemically synthesized oligosaccharides.

A new ex vivo method for assaying adhesion of cancer cells to the greater omentum has been developed using mouse greater omentum and [3H]labelled human gastric and mouse colorectal cancer cells. Since the adhesion rates were found to increase up to 18 h and labelled cells seemed to be stable during the period, the present method could be useful for investigating adhesion of cancer cells to the greater omentum, which must occur at the first step of the peritoneal dissemination. The adhesion of cancer cells to the greater omentum was inhibited by a series of chemically synthesized oligosaccharides and Gal beta1,3[3OMeGal beta1,4GlcNAc beta1,6]alphaBn was found to be the best inhibitor. The anti-tumor effect of this novel tetrasaccharide in vivo was shown in preliminary experiments using Balb/c mice and colon26 cells.

Animals↗

Early colorectal cancer: flat or depressed type.

The present review describes the changes in views about the early forms of colorectal cancers. In 1985, a concept of 'flat adenoma' was born in Japan. At around the same time, depressed type early colorectal cancers started to be reported by Japanese colonoscopists. Neither flat adenomas nor depressed lesions have been frequently reported in Western countries, but increasing numbers of such cases are now described. The problem is that flat adenomas and depressed lesions seem to have been confused by many researchers. The biological aggressiveness of these lesions is quite different. The rate of submucosal invasion is very high in depressed lesions, but fairly low in small flat adenomas. Some adenomas may even look depressed at first, but such lesions should not be mistaken for truly depressed lesions. Ignorance or resistance to the concept may inhibit the detection of flat or depressed lesions. Differences of diagnostic criteria between Japanese and Western pathologists may influence the apparent frequency of mucosal cancers, but not that of invasive carcinomas. Many small adenomas do not grow if followed, but depressed lesions grow rapidly and invade the deeper layers and, as a result, may look elevated as a whole. Many cases in previously published papers suggest that small depressed carcinomas of the large intestine may develop without a precursory stage of an adenomatous polyp. At least two carcinogenic pathways, one through adenomatous polyps and one de novo, should be recognized. In addition, the importance of small depressed cancers should be emphasized.

Adenoma↗

Chlamydia pneumoniae in atherosclerotic and nonatherosclerotic tissue.

The positivity rate and localization of Chlamydia pneumoniae were investigated in atherosclerotic and nonatherosclerotic tissues by immunohistochemistry, polymerase chain reaction, and cell culture. In total, 67 atheromatous plaques from Japanese symptomatic patients and 110 nonatherosclerotic tissues and organs were evaluated. Of these, 62% of atherosclerotic plaques from symptomatic patients were infected with C. pneumoniae compared with just 2% of nonatherosclerotic tissues. Immunohistochemically stained C. pneumoniae were found most often in smooth muscle cells, less often in macrophages, and in a few endothelial cells.

Adult↗

Breast masses with peripheral rim enhancement on dynamic contrast-enhanced MR images: correlation of MR findings with histologic features and expression of growth factors.

PURPOSE: To investigate the histologic bases of rim enhancement of breast masses demonstrated on dynamic contrast material-enhanced magnetic resonance (MR) images. MATERIALS AND METHODS: Dynamic MR images of breast lesions (invasive carcinoma, n = 29; other, n = 6) in 35 women were reviewed. In each patient, subtraction images of the dynamic contrast-enhanced study were obtained, and early and delayed rim enhancement and delayed internal enhancement were evaluated. The MR findings were correlated with the ratio of microvessel density of the peripheral to the central portion of the lesion, fibrosis, and other histologic features, including expression of vascular endothelial growth factor (VEGF) and transforming growth factor ss1. RESULTS: Early rim enhancement was observed in 29% and delayed rim enhancement was noted in 60% of all patients. Small cancer nests, a high ratio of peripheral-to-central microvessel density, peripheral VEGF expression, and a low ratio of peripheral-to-central fibrosis were correlated with early rim enhancement. Delayed rim enhancement was correlated with a high degree of fibrosis and inflammatory changes. Delayed internal enhancement was correlated with a high degree of fibrosis. CONCLUSION: Rim enhancement of breast lesions at MR imaging is due to a combination of angiogenesis, distribution and degree of fibrosis, expression pattern of VEGF, and various histologic features.

Adenocarcinoma, Mucinous↗

The effects of soybean transphosphatidylated phosphatidylserine on cholinergic synaptic functions of mice.

The effects of soybean transphosphatidylated phosphatidylserine (SB-tPS) on cholinergic synaptic functions were investigated using cerebral cortical synaptosomes from mice. Treatment of the synaptosomes with SB-tPS increased high K+-induced acetylcholine (ACh) release in a bell-shaped, dose-dependent manner without affecting ACh synthesis. SB-tPS (10 and 50microM) also enhanced synaptosomal synthesis of sn-glycero-3-phosphocholine, but did not affect phosphorylcholine synthesis. In contrast, the choline synthesis was significantly reduced as SB-tPS concentration increased. The present result that SB-tPS modified the cholinergic pathway can partly explain its nootropic functions.

Acetylcholine↗

Enzymatic properties of phenylalanine101 mutant enzyme of ribonuclease rh from Rhizopus niveus.

To investigate the role of Phe101, a component of a base recognition site (B2 site) of a base-nonspecific RNase Rh from Rhizopus niveus, we prepared several enzymes mutated at this position, F101W, F101L, F101I, F101A, F101Q, F101R, and F101K, and their enzymatic activities towards RNA, 16 dinucleoside phosphates, and 2', 3'-cyclic pyrimidine nucleotides were measured. Enzymatic activity toward RNA of F101W, F101L, and F101I were about 7, 20, and 3.8% of the native enzyme, respectively, and those of the other mutants were less than 1% of the RNase Rh. Similar results were also obtained with GpG as substrate. Thus, it was concluded that Phe101 is a very important residue as a component of the B2 site of RNase Rh, and its role could be replaced by Leu, then Trp and Ile, though in less effectively. The results suggested that some kind of interaction between B2 base and the side chain of amino acid residue at the 101th position, such as pi/pi or CH/pi interaction is very important for the enzymatic activity of RNase Rh. The mutation of Phe101 markedly affected the enzymatic activity toward dinucleoside phosphates and polymer substrates, but only moderately the rate of hydrolysis of cyclic nucleotides, indicating the presence of secondary effect of the mutation on B1 site.

Base Sequence↗

Inhibition of chondrogenesis by parathyroid hormone in vivo during repair of full-thickness defects of articular cartilage.

We studied the effects of parathyroid hormone (PTH) on differentiation of chondroprogenitor cells during the repair of full-thickness articular cartilage defects. Three-millimeter cylindrical full-thickness articular cartilage defects, which are small enough to be resurfaced spontaneously by hyaline cartilage, were created in the femoral trochlea of the rabbit knee. Recombinant human PTH(1-84) (hPTH[1-84]) (25 ng/h) then was administered into the joint cavity with an osmotic pump, or in control animals, saline alone was administered. The animals were killed at 1, 2, 4, and 8 weeks. At 1 week, the defects were filled with undifferentiated cells, regardless of the PTH treatments. By 8 weeks, well-developed cartilage covered the defects with reconstitution of subchondral bone up to the original bone-articular cartilage junction. In contrast, no evidence of chondrogenic differentiation was seen at any time during the experimental period in the defects treated with PTH. The reparative tissues also were examined immunohistochemically using anti-proliferating cell nuclear antigen (PCNA) and anti-PTH/PTH-related peptide (PTHrP) receptor antibodies. Interestingly, the chondroprogenitor cells that filled the defects expressed PTH/PTHrP receptor, suggesting that these cells are capable of responding to PTH/PTHrP signaling before overt chondrogenesis. Application of PTH did not interfere with proliferation but inhibited chondrogenic differentiation of the cells resulting in the formation of fibrous tissue that lost the expression of PTH/PTHrP receptor within 4 weeks.

Animals↗

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 23). A comparative 2- and 4-week repeated oral dose testicular toxicity study of boric acid in rats.

To assess the validity and limitations of 2-week repeated daily dosing to detect toxic effects on male reproductive organs in rodents, a comparative 2- and 4-week oral repeated dosing study of boric acid, a known testicular toxicant, was given to 6- or 8-week-old Crj:Wistar rats at daily levels of 0, 125, 250 and 500 mg/kg. The ages of the rats were selected so that they were all sacrificed at 10 weeks of age. The testes and epididymides were weighed at necropsy; histopathological specimens were prepared in a routine manner and stained with H&E or PAS-H. In addition, the sperm number and motility rates were evaluated. There were no boric acid-induced effects on reproductive organ weights and on gross behavior/appearance in any groups in either the 2- or 4-week studies. The sperm number and motility rate were not decreased in any group after 2 weeks, while both decreased in the 250 and 500 mg/kg groups after 4 weeks. Histopathologically, as evidence of toxicity at the early stage of boric acid exposure, retention of step 19 spermatids of stages IX-XI was observed in the testes of almost all rats treated with 500 mg/kg after both 2 weeks and 4 weeks. Degenerative/necrotic germ cells and multinucleated giant cell formation were observed in 2 weeks, though to a lesser extent than in 4 weeks. On stage analysis of germinal cells in 2 weeks, spermatogonia and spermatids of stage VII were found to be decreased, and pachytene spermatocytes of stage X were increased. In conclusion, the results indicate that if the selection of doses is appropriate, testicular toxicity of boric acid can be detected even after only 2 weeks of repeated daily oral treatment.

Administration, Oral↗

Acute fatty liver of pregnancy showing microbial infection in the liver.

A 24-year-old, nulliparous woman in her 30th week of pregnancy was admitted due to threatened premature delivery. Ritodrin chloride relieved the premature contraction of the uterus but jaundice and drowsiness appeared 7 weeks later. Laboratory data revealed disseminated intravascular coagulation (DIC) with intrahepatic cholestasis, and ultrasound examination showed fatty liver. The patient was diagnosed with acute fatty liver of pregnancy (AFLP). Emergency delivery by Caesarean section was performed at 37 weeks of pregnancy and the liver function and DIC improved immediately. Liver biopsy 13 days after delivery showed nuclear swelling and cytoplasmic ballooning with mild fatty deposition. These findings were relatively compatible with acute AFLP. Higher magnification and electron microscopy revealed intracytoplasmic bacteria and fungus in the residual stage. The bacterial infection could be considered related to AFLP.

Acute Disease↗

A method for identifying underlying causes of death in epidemiological study.

To obtain the underlying causes of death in individuals of a cohort (male only), the items of date of birth, date of death and address code at the time of death were linked between the data of resident cards and the death tapes of National Vital Statistics supplied by the Ministry of Health and Welfare. As a result, the persons who have the same information for above mentioned three items between the resident cards and the death tapes accounted for 97.4%. If the persons who had the same information for three items except one item were considered to be identical, they accounted for 99.4%. It would be concluded that underlying cause of death can be obtained by record linkage of death tapes of National Vital Statistics with three informations in residence cards, dates of birth, dates of death and address codes at the time of death, even without names of the individual in the death tapes. The matched rate would be high enough for epidemiological studies.

Cause of Death↗

Use of a temporary caval filter in a young man with pulmonary embolism to prevent migration of massive caval thrombus during an attempt of caval thrombolysis.

A 33 year old male with no known risk factors for hypercoagulability developed a massive thrombi in the inferior vena cava (IVC). The patient had a history of both pulmonary embolism and embolism related syncope. The thrombus which extended proximally to the level of the renal vein and distally to the left superficial femoral vein did not respond to anticoagulant therapy or thrombolysis. Thirteen days after admission, we decided to use a temporary caval filter to provide protection from migration of the thrombus while attempting invasive thrombolytic therapy, which was performed using a tissue type plasminogen activator through a coaxial catheter of the temporary filter. This resulted in a marked decrease in the size of the thrombus, and multiple thrombi were found to be trapped in the temporary filter. Although the temporary caval filter was effective in capturing emboli, resulting in a decrease in the thrombus size, the thrombus was not completely dissolved within two weeks, which is the maximal implantation time. A permanent filter was eventually used to prevent pulmonary embolism, which could arise from the remaining thrombus. We have found placement of a temporary caval filter to be a safe and effective adjunct, in select cases, when attempting thrombolysis of massive thrombi in the IVC. Since we inserted the temporary filter 13 days after admission, use of a temporary filter during thrombolysis may have been more effective if conducted earlier in our patient's clinical course.

Adult↗

Phenacetin deacetylase activity in human liver microsomes: distribution, kinetics, and chemical inhibition and stimulation.

Microsomal and cytosolic phenacetin deacetylase activities were examined in human liver and kidneys. Kinetic properties of the activities were also studied in human liver microsomes. Phenacetin deacetylase activity was predominantly localized in the liver microsomal fraction. The specific activities of phenacetin deacetylation in liver cytosol and in kidney microsomes and cytosol were all less than 5% of that in liver microsomes. In human liver microsomes, Eadie-Hofstee plots for phenacetin deacetylation were monophasic, indicating a single-enzyme catalytic reaction. The Michaelis-Menten parameters, K(m) and V(max), for the deacetylation were 4.7 mM and 5.54 nmol/min/mg of protein, respectively. The intrinsic clearance, calculated as V(max)/K(m), was 1.18 microl/min/mg of protein. Although the organophosphate bis(4-nitrophenyl)phosphoric acid markedly inhibited the reaction in human liver microsomes, the activity has a tolerance to the treatment of phenylmethylsulfonyl fluoride, a serine hydrolase inhibitor. Prazosin, a peripheral alpha(1)-adrenergic antagonist, noncompetitively inhibited the phenacetin deacetylation with a K(i) value of 19.0 microM. Flutamide, a nonsteroidal androgen receptor antagonist, stimulated the activity by up to 349%. This increase was accompanied by a decrease in the K(m) value and no change in the V(max) value, resulting in an increase in the intrinsic clearance by up to 700% of the control. These results suggest that the phenacetin deacetylase localized in human liver microsomes has not only a catalytic site but also a negative and/or positive modulation site or sites.

Carboxylic Ester Hydrolases↗

Oxidative cleavage of the octyl side chain of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045) in rat and dog liver preparations.

The metabolism of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045), a new potent biguanide antiseptic, was investigated using rat and dog liver preparations to elucidate the mechanism of OPB-2045 metabolite formation, in which the octyl side chain is reduced to four, five, or six carbon atoms. Chemical structures of metabolites were characterized by 1H NMR, fast atom bombardment/mass spectrometry, and liquid chromatography/electrospray ionization-tandem mass spectrometry. Three main metabolites were observed during incubation of OPB-2045 with rat liver S9: 2-octanol (M-1), 3-octanol (M-2), and 4-octanol (M-3). In the incubation of OPB-2045 with dog liver S9, eight metabolites were observed, seven of which being M-1, M-2, M-3, 2-octanone (M-4), threo-2,3-octandiol (M-5), erythro-2,3-octandiol (M-6), and 1,2-octandiol (M-7). M-5 and M-6 were further biotransformed to a ketol derivative and C-C bond cleavage metabolite (hexanoic acid derivative), an in vivo end product, in the incubation with dog liver microsomes. The reactions required NADPH as a cofactor and were significantly inhibited by the various inhibitors of cytochrome P450 (i.e., CO, n-octylamine, SKF 525-A, metyrapone, and alpha-naphthoflavone). The results indicate that the degraded products of OPB-2045 are produced by C-C bond cleavage after monohydroxylation, dihydroxylation, and ketol formation at the site of the octyl side chain with possible involvement of cytochrome P450 systems. This aliphatic C-C bond cleavage by sequential oxidative reactions may play an important role in the metabolism of other drugs or endogenous compounds that possess aliphatic chains.

Animals↗