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Biomedical subjects

K Yokota

Publications and source records attributed to K Yokota.

At least 163 records · Page 9Linked to original sources

[Diffuse tracheobronchial amyloidosis with airflow limitation and repeated pneumonias].

A 67-year-old man was first admitted to our hospital complaining of a productive cough, and repeated episodes of pneumonia in different sites. Physical examination revealed expiratory wheezing and airflow limitation wlas documented with lung function tests. A chest X-ray film showed patchy pneumonic infiltrates. Chest computed tomography revealed a marked thickening of the tracheal and bronchial wall with linear calcification. Fiberoptic bronchoscopy revealed a diffuse infiltrative process in the tracheobronchial tree, which uniformly reduced the bronchial lumen. Bronchial biopsy specimens showed amyloid deposits with focal calcification, which was confirmed by Congo red and Dylon staining. Extensive examinations including rectal biopsy were negatie for systemic amyloidosis. We suggest that diffuse tracheobronchial amyloidosis should be included in the differential diagnosis of repeated pulmonary infections with airflow obstruction.

Aged↗

[Effects of gonadotropin-releasing hormone and its analogue (buserelin) on aromatase in cultured human granulosa cells].

We studied the direct effects of gonadotropin-releasing hormone (GnRH) and its analogue (buserelin) on aromatase activity and the aromatase cytochrome P-450 (P-450arom) concentration in cultured human granulosa cells which were obtained during oocyte retrieval for in vitro fertilization. Aromatase activity was assessed by radioassay with [1beta-3H]androstenedione as the substrate. The P-450arom concentration was determined by an enzyme-linked immunosorbent assay with specific antibodies to P-450arom. Buserelin stimulated aromatase activity and P-450arom at low concentrations (10(-13) - 10(-9)M), but it suppressed these parameters at high concentrations (10(-8) - 10(-7)M). The stimulatory effect increased with time during 12- to 48-h culture and disappeared after 72-h culture. Follicle-stimulating hormone (FSH) (100 ng/ml) stimulated aromatase activity and the P-450arom concentration but, FSH stimulation was suppressed by co-administration of low or high concentrations of buserelin. In contrast GnRH suppressed aromatase activity and P-450arom at all concentrations (10(-12) - 10(-6)M). GnRH also suppressed FSH stimulation of aromatase. Aromatase activity was correlated with the P-450arom concentration. These results suggest that in human preovulatory granulosa cells, buserelin and GnRH modulate aromatase activity by changing the P-450arom concentration.

Aromatase↗

cDNA cloning of a new putative ATPase subunit p45 of the human 26S proteasome, a homolog of yeast transcriptional factor Sug1p.

The nucleotide sequence of a cDNA that encodes a new regulatory subunit, named p45, of the 26S proteasome of human hepatoblastoma HepG2 cells has been determined. The polypeptide predicted from the open reading frame consists of 406 amino acid residues with a calculated molecular weight of 45770 and isoelectric point of 8.35. The sequences of several fragments of bovine p45, determined by protein chemical analyses, spanning 27% of the complete structure, were found to be in excellent accord with those deduced from the human cDNA sequence. Computer analysis showed that p45 belongs to a family of putative ATPases which includes regulatory components of 26S proteasomes. The overall structure of p45 was found to be homologous to that of yeast Sug1p, which has been identified as a transcriptional factor. It is closely similar, but not identical to the sequence reported for Trip1, a functional homolog of Sug1p in human tissues. These results are consistent with the possibility that Sug1-like proteins with distinct sequence function in transcription and protein degradation in human cells. However, the alternative hypothesis, that the same gene locus encodes both p45 and Trip1, cannot be excluded on the basis of such closely similar sequences. In either case, both proteins are likely to function equivalently well in either transcription or protein degradation.

Adenosine Triphosphatases↗

Macromolecular ionophores. 1. Chiral recognition properties of poly[(1-->6)-2,5-anhydro-D-glucitol] toward racemic amino acid ester.

The chiral recognition property of poly[(1-->6)-2,5-anhydro-3,4-di-O-alkyl-D-glucitol] (1) toward racemic RCH (CO2CH3)NH3+.PF6- (2.HPF6) has been studied using a transport system involving an aqueous source and receiving phases separated by a chloroform phase containing 1. Transport rates for aromatic guests 2a (R = Ph) and 2b (R = CH2Ph) were faster than those for aliphatic guests, 2c (R = CH(CH3)2) and 2d (R = CH2CH(CH3)2), using the polymer substituted with methyl groups (1a). The enantiomeric excess (e.e.) was 10.9% for 2a as a maximum value and decreased in the order of 2a > 2c > 2b = 2d. When the transport of 2a.HPF6 was carried out using the polymers with 3,4-di-O-methyl (1a), ethyl (1b), allyl (1c), and pentyl (1d) groups, the e.e. was 22.0% for 1d as a maximum value and increased in the order of 1a < 1b < 1c < 1d. The formation of a complex between 1a and 2a.HPF6 was confirmed by 1H and 13C NMR spectral measurements.

Amino Acids↗

Association between elevated plasma granulocyte colony-stimulating factor and the degree of surgical stress in patients undergoing gastrointestinal surgery.

To characterize the changes in perioperative plasma granulocyte colony-stimulating factor (G-CSF) and analyze the effect of surgical stress on its kinetics, 41 patients undergoing gastrointestinal surgery with varying degrees of surgical stress were examined. The plasma levels of G-CSF significantly increased immediately after the operation, probably in response to surgical injury. This elevation was much higher in the 15 esophagectomy patients, at 883 +/- 300 pg/ml on postoperative day (POD) O, than in the 14 gastrectomy patients, with a value of 233 +/- 151 on POD O, (P < 0.01) or in the 12 cholecystectomy patients, with a value of 64 +/- 41 on POD 1 (P < 0.01). These findings led us to conclude that G-CSF levels increase significantly in the immediate postoperative period and are most likely associated with the degree of surgical stress. In addition, we studied the priming effect of G-CSF on polymorphonuclear leukocytes (PMNs). G-CSF enhanced PMN superoxide anion (O2-) production and luminol-dependent chemiluminescence (CL) induced by opsonized zymosan in a dose-dependent manner. A significant enhancement was seen in the G-CSF level (1 ng/ml) which was almost the same as the maximum G-CSF level in the esophagectomy patients. Furthermore, postoperative PMN activation occurred after the elevation of plasma G-CSF. Thus, we propose that elevated G-CSF may act as one of the mediators which activate PMN function postoperatively.

Aged↗

Characterization of Streptococcus sanguis isolated from patients with Behçet's disease.

The DNA homology and cell wall sugar constituents of eight Streptococcus sanguis(-like) strains, three isolated from the patients with Behçet's disease (BD114-23, BD113-20, BD118-1), two from patients with Kawasaki disease (MCLS-1, MCLS-2), and three type and reference strains of ATCC (ATCC10556T: S. sanguis, ATCC10557: S. oralis, and ATCC10558T: S. gordonii) were analyzed. Strains BD114-23 and BD118-1 showed high DNA homology to ATCC10556T, and their cell wall constituents were identical. Conversely, BD113-20, MCLS-1, MCLS-2, and ATCC10557 showed little DNA homology to ATCC10556T and ATCC10558T, but showed approximately 50 to 60% homology to each other. The cell wall constituents of BD113-20, MCLS-1, MCLS-2, and ATCC10557, however, were somewhat different, indicating that some of the clinical isolates have different characters from those of the three ATCC strains.

Behcet Syndrome↗

Satisfactory remission achieved by PUVA therapy in a case of crisis-type adult T-cell leukaemia/lymphoma with generalized cutaneous leukaemic cell infiltration.

We used PUVA therapy in a patient with crisis-type adult T-cell leukaemia/lymphoma and generalized cutaneous leukaemic cell infiltration. PUVA proved very effective in reducing leukaemic cells and in clearing the eruption. To understand the way in which PUVA produced a reduction in the number of leukaemic cells, we examined peripheral blood cells by light and electron microscopy. Light microscopy was of little help, but electron microscopy revealed that PUVA induced apoptosis-like changes in circulating leukaemic cells. This suggests that apoptosis-like changes in leukaemic cells might be the reason for the success of this treatment.

Apoptosis↗

Role of Ca2+ on endotoxin-sensitivity by galactosamine challenge: lipid peroxide formation and hepatotoxicity in zymosan-primed mice.

This study was investigated to clarify the role of intracellular Ca2+ following endotoxin treatment (1 mg/kg, intraperitoneally) to D-galactosamine-sensitized mice (400 mg/kg, intraperitoneally), and to observe lipid peroxide levels, an index of hepatotoxicity, in endotoxin/galactosamine (Ga1N)-challenged mice under activation of macrophages, especially Kupffer cells, by zymosan. The liver lipid peroxide level and serum glutamic pyruvic transminase activity in mice 18 hr after administration of endotoxin/Ga1N were markedly higher than those in mice treated only with endotoxin. In spite of an increase in lipid peroxide formation, there was little or no effect of Ga1N administration on xanthine oxidase and superoxide dismutase activities in mice given endotoxin. However, the injection of verapamil (10 mg/kg, subcutaneously) markedly decreased lipid peroxide levels in liver of endotoxin/Ga1N-injected mice. In the mice given a Ca(2+)-deficient diet, lipid peroxide level in liver after endotoxin/Ga1N injection was markedly decreased compared to that in mice fed a normal diet. Administration of dexamethasone (200 micrograms/kg, intraperitoneally) in mice 1 hr before treatment with endotoxin/Ga1N did not induce lipid peroxide formation. Administration of endotoxin to Ga1N-treated mice resulted in a higher level of liver cytosolic free Ca2+ ([Ca2+]i) than that in endotoxin-treated mice. On the other hand, Ca(2+)-ATPase activity in liver plasma membrane in the endotoxin/Ga1N-treated mice was markedly decreased as compared with endotoxin alone. On the contrary, the Ca(2+)-ATPase activity in liver mitochondria was higher in endotoxaemic mice treated with GA1N than in mice given endotoxin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Effect of KBT-3022, a new diphenylthiazole derivative, on platelet functions.

The effects of KBT-3022 and its metabolite desethyl KBT-3022 on platelet aggregation were determined in rat, guinea-pig, rabbit and human platelets in-vitro and ex-vivo. KBT-3022 and desethyl KBT-3022 inhibited platelet aggregation induced by arachidonic acid and collagen in-vitro more potently than aggregation induced by adenosine diphosphate, platelet-activating factor or thrombin, as well as by acetylsalicylic acid, and their effects were approximately 100 times more potent than those of acetylsalicylic acid. Desethyl KBT-3022, but not KBT-3022 or acetylsalicylic acid, inhibited thrombin-induced aggregation and 5-hydroxytryptamine release from platelets more potently than ticlopidine hydrochloride at higher concentrations. Oral administration of KBT-3022 inhibited both arachidonic acid- and collagen-induced platelet aggregation and reduced platelet retention in a glass-bead column approx. 100 times more potently than acetylsalicylic acid. KBT-3022 showed little or no anti-inflammatory effect on either ultraviolet-induced erythema or arachidonic acid induced ear oedema, and had lower gastro-ulcerogenicity than acetylsalicylic acid. These results suggest that KBT-3022 is a potent inhibitor of platelet activation with weak side-effects.

Adenosine Diphosphate↗

Unique cholesteryl glucosides in Helicobacter pylori: composition and structural analysis.

A chloroform-methanol-extracted lipid of Helicobacter pylori was studied. Three kinds of glycolipids, accounting for about 25% (wt/wt) of the total lipid, were detected and identified to be cholesteryl glucosides. The structures of two of them were determined to be cholesteryl-alpha-D-glucopyranoside and cholesteryl-6-O-tetrade-canoyl-alpha-D-glucopyranoside, and the plausible structure of the third one was identified as cholesteryl-6-O-phosphatidyl-alpha-D-glucopyranoside. Cholesteryl glucosides are very rare in animals and bacteria. Furthermore, those in H. pylori had an alpha-glycosidic linkage, which is rather unusual for natural glycosides, and a phosphate-linked cholesteryl glycoside like the cholesteryl-6-O-phosphatidyl-alpha-D-glucopyranoside has not been reported previously. As the cholesterol glucosides were detected in strains obtained from diverse geographical locations, the presence of cholesteryl glucosides in H. pylori is a very unique and a characteristic feature of the species. These findings add a new facet to the physiology and biochemistry, especially the cholesterol and glucose metabolism, of H. pylori. Furthermore, the cholesteryl glucosides of H. pylori showed hemolytic activities.

Cholesterol↗

Steryl glycosides: a characteristic feature of the Helicobacter spp.?

The lipids of different species of Helicobacter (H.felis, H. muridarum, H. mustelae, H. fennelliae, and H. cinaedi) were studied. Different types of cholesteryl glucosides were found in all of the species studied except H. cinaedi. The total amount of cholesteryl glucosides varied from 14.8% of total lipids in H. mustelae to 33.1% of total lipids in H. felis. The different types of cholesteryl glucosides and their species distribution are cholesteryl-6-O-acyl-alpha-D-glucopyranoside (cholesteryl-6-O-tetradecanoyl-alpha-D-glucopyranoside in H. felis and cholesteryl-6-O-dodecanoyl-alpha-D-glucopyranoside in H. muridarum), cholesteryl-alpha-D-glucopyranoside (H. felis, H. muridarum, H. mustelae, and H. fennelliae), and cholesteryl-6-O-phosphatidyl-alpha-D-glucopyranoside (H. fennelliae). The neutral lipid fractions showed a high percentage of cholesterol, with selective accumulation of free cholesterol. The study thus shows that the characteristic presence of steryl glycosides in Helicobacter spp. may be an important chemotaxonomic marker for many of the species, and the helicobacters show a selective accumulation of free cholesterol from the media.

Cholesterol↗

Depressive effect of a traditional Chinese medicine (sho-saiko-to) on endotoxin-induced nitric oxide formation in activated murine macrophage J774A.1 cells.

The present study investigated whether or not Sho-saiko-to (crude powder extract, TJ-9) can suppress nitric oxide (NO) generation by endotoxin-activated J774A.1 cells in order to study the preventive mechanism of Sho-saiko-to against endotoxemia. In this experiment, we estimated the NO2- in the murine macrophage cell line J774A.1 using the Griess method. Our results clearly demonstrated that J774A.1 cells stimulated with endotoxin (0.01-10 micrograms/ml) can effectively produce NO, and the production was dependent on the dose of endotoxin. On the other hand, we investigated the suppressive effect of TJ-9 (10-100 micrograms/ml) on NO generation by endotoxin (0.1 microgram/ml)-activated J774A.1 cells. The NO level when the cells were incubated with endotoxin and TJ-9 (10-20 micrograms/ml) was slightly lower than that in cells treated with endotoxin alone. In contrast, treatment with TJ-9 (50-100 micrograms/ml) significantly inhibited endotoxin-activated NO generation in J774A.1 cells, whereas the treatment with TJ-9 (10-100 micrograms/ml) alone was ineffective in inducing NO formation and in inhibiting cell viability in the J774A.1 cells. These findings suggest that a Kampo presciption of Sho-saiko-to shows a suppressive effect on NO generation in macrophages stimulated with endotoxin, and that it may be useful in improving endotoxin-shock symptoms.

Animals↗

Anti-thrombotic activity of KBT-3022 in experimental models of thrombosis.

In this study, we investigated the effects of KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)-thiazol-2-yl]pyrrol-1-ylacetate) , a potent and long-lasting anti-platelet agent, in several experimental thrombosis models and compared them with those of other anti-platelet drugs. Oral administration of KBT-3022 prevented arachidonic acid-induced death due to pulmonary embolism in mice and rabbits with respective ED50 values of 0.29 and 0.12 mg/kg. The protective effect of acetylsalicylic acid (ASA) against mortality was weaker than that of KBT-3022, and ticlopidine hydrochloride (TP) showed no such effect in these models. In a guinea pig arterio-venous shunt model, the inhibition by KBT-3022 of thrombus formation on a silk thread inserted into the shunt was dose-dependent and 300 and 30 times more potent than the inhibition obtained with ASA and indomethacin, respectively. In a model of aortic thrombosis induced by perivascular application of 20% silver nitrate solution, KBT-3022 (1 mg/kg, p.o.) inhibited thrombus formation significantly, ASA (100 mg/kg, p.o.) tended to inhibit it, and TP had no effect. However, in a stasis-induced venous thrombosis model in guinea pigs, TP inhibited thrombus formation significantly, but KBT-3022 and ASA were ineffective. These results suggest that KBT-3022 may be a useful drug for the treatment and/or prophylaxis of thrombus formation in shunts and aortic thrombosis.

Animals↗

Inhibitory effect of KBT-3022, a new anti-platelet agent, on infiltration of polymorphonuclear leukocytes induced by leukotriene B4 or formyl-methionyl-leucyl-phenylalanine in mice.

We devised a method for evaluating polymorphonuclear leukocyte (PMN) infiltration in vivo employing an air bleb technique combined with measurement of myeloperoxidase (MPO) activity, and the effects of some anti-platelet agents were evaluated. KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) and cilostazol inhibited the increase in MPO activity in the connective tissue around the air bleb induced by leukotriene B4 (LTB4) and formyl-methionyl-leucyl-phenylalanine (fMLP). Indomethacin inhibited only the fMLP-induced increase in MPO activity, but ticlopidine hydrochloride and acetylsalicylic acid had no effect. Histologic observation confirmed the inhibition of PMN infiltration by KBT-3022. These results indicate that KBT-3022 may be a potent inhibitor of both LTB4- and fMLP-induced infiltration of PMNs.

Animals↗

Protective effect of KBT-3022, a new cyclooxygenase inhibitor, in cerebral hypoxia and ischemia.

The protective effect of KBT-3022 (ethyl 2-[4,5-bis-(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) , a new cyclooxygenase inhibitor, in cerebral hypoxia and ischemia was studied and compared with those of indomethacin and acetylsalicylic acid (ASA). Oral administration of KBT-3022 (3-100 mg/kg) and indomethacin (3 and 10 mg/kg) significantly prevented KCN-induced death in mice, while ASA (100 mg/kg) had no effect. KBT-3022 (3 and 10 mg/kg, p.o.) and indomethacin (10 mg/kg, p.o.) significantly prolonged the survival time of mice subjected to normobaric hypoxia, while ASA (100 mg/kg, p.o.) had no effect. KBT-3022 (3-30 mg/kg, p.o.) and indomethacin (3 mg/kg, i.p.) significantly ameliorated delayed neuronal death in the gerbil hippocampal CA1 sector after occlusion of bilateral carotid arteries for 5 min, while ASA (300 mg/kg, p.o.) had no effect. KBT-3022 (10 mg/kg, p.o.) significantly inhibited ATP depletion in the gerbil hippocampus after a 1-min occlusion of bilateral carotid arteries, but had no effect on ATP depletion after a 5-min occlusion and the recovery during recirculation. These results show that KBT-3022 exerts protective effects against cerebral anoxia and hypoxia and ameliorates delayed neuronal death in the hippocampus. KBT-3022 may therefore be useful for prophylaxis of ischemic cerebrovascular disorders.

Adenosine Triphosphate↗

Activation mechanism of phospholipase D involved in the generation of lipid mediators in cultured Madin-Darby canine kidney cells.

Addition of 100 nM phorbol 12-myristate 13-acetate (PMA), an active phorbol diester, to quiescent cultured Madin-Darby canine kidney (MDCK) cells caused a maximal stimulation of phosphatidylethanol formation within 1-2 h in the presence of 1% ethanol, indicating the activation of phospholipase D (PLD). The specificity of phorbol diesters for the activation of PLD activation was confirmed by the fact that phorbol 12,13-dibutyrate (PDBu) was effective, whereas 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD) was without effect. Down-regulation caused by the long-term pretreatment of the cells with active phorbol diesters significantly decreased the production of phosphatidylethanol. Staurosporine, a well known protein kinase (PK)C inhibitor at 1 microM, decreased the activation of PLD. Taken together, these observations suggested the involvement of PKC in the activation of PLD. The cellular PLD activity was found to be selectively localized in the particulate fraction by centrifugation at 12,000 x g. The particulate PLD showed the selective substrate specificity for phosphatidylcholine rather than phosphatidylethanolamine. In response to the addition of 100 nM PMA, 1,2-diacylglycerol (DG) increased in a biphasic fashion. In view of the time course of the activation of PLD, the second increase in the 1,2-DG around 20 min was contributed by the activation of PLD. In response to the simultaneous addition of 100 nM PMA and 100 nM A23187, the cultured MDCK cells activated the arachidonate cascades to form prostaglandin (PG)E2 and PGF2 alpha as major products, requiring slower 24 h to reach maximal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lipid profiles of Helicobacter pylori and Helicobacter mustelae grown in serum-supplemented and serum-free media.

Many of Helicobacter species have been found to have novel cholesteryl glucosides (CGs). To study the biosynthetic mechanism of CGs, the lipid profiles of H. pylori and H. mustelae grown in serum-supplemented and cholesterol-restricted serum-free media were investigated. In contrast to the serum-supplemented state, helicobacters had less CGs in the serum-free state; a trace amount of CGs and no CG was detected in H. pylori and H. mustelae, respectively. The proportion of total and individual phospholipid also showed significant alteration. Unknown lipids which did not contain phosphate and sugar were detected in the serum-free state, but not in the serum-supplemented state. The CGs were found to be distributed mainly in the membrane fractions, and one of the unknown lipids was found exclusively in the cytosol fraction. Based on these data, it is apparent that the CGs of helicobacters are synthesized by de novo uptake of cholesterol from the media. The unknown lipids detected in the serum-free state may be storage lipids, appearing in response to depletion of nutrients, especially cholesterol, or other factors in the media.

Culture Media↗

[Endoscopic treatment of esophageal and gastric cancers].

Since 1978 we have applied various endoscopic procedures to esophageal and gastric malignancies for a palliative or a radical purpose. An outline of our experience was presented herein. Endoscopic Laser irradiation has been given to 61 cases (64 lesions) of early gastric cancers as a radical treatment since 1978. The irradiation was repeated once a week until getting disappearance of cancer cells in biopsy specimens. The Laser irradiation has also been given to 13 cases of advanced gastric cancers since 1978 and 12 cases of advanced esophageal cancers since 1985 for palliative purposes, such as, mass reduction, hemostasis, and removals of stenosis or obstruction. From 1991 the endoscopic mucosal resection (EMR) method has been used to 75 cases (93 lesions) as a radical treatment for gastric adenomas (n = 24) and well-differentiated adenocarcinomas less than 2 cm in size without ulceration (n = 69). The endoscopic Laser irradiation for early gastric cancers showed a survival rate of 62.8% after 5 years. The recurrence was preferentially found in depressed cancers and polypoid cancers of more than 3 cm in size, and often appeared within one year after the treatment. The Laser treatment for advanced gastric and esophageal cancers showed a survival rate of 69% and 33% after 6 months, respectively. In many cases, subjective symptoms like gastric bleeding or dysphasia were markedly improved after the treatment. The complete removal of gastric tumors was obtained at 65% with the conventional strip biopsy method, and at 80% with the double snare polypectomy or EMR using the EVL device.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗