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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 91 records · Page 5Linked to original sources
PubMed2001

Desferrioxamine, an iron chelator, upregulates cyclooxygenase-2 expression and prostaglandin production in a human macrophage cell line.

Prostaglandins (PGs) play regulatory roles in a variety of physiological and pathological processes, including the immune response, cytoprotection and inflammation. Desferrioxamine (DFX), an iron chelator, is known to reduce free radical-mediated cell injury and to upregulate certain inflammatory mediators. We investigated the effects of DFX on the production of PGs and the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of PGs, using a human macrophage cell line, U937. Our results showed that COX-2 expression and PGE(2) production are upregulated by DFX treatment and that this upregulation is dependent on both COX-2 promoter activity and alteration of mRNA stability. COX-2 promoter activity may be, at least in part, mediated by activation of the extracellular signal-regulated kinase pathway. These findings suggest that iron metabolism may regulate inflammatory processes by modulating PGs as well as other inflammatory mediators.

Binding Sites↗
PubMed2001

3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors block calcium-dependent tyrosine kinase Pyk2 activation by angiotensin II in vascular endothelial cells. involvement of geranylgeranylation of small G protein Rap1.

We recently reported the calcium-dependent activation of tyrosine kinase Pyk2 by angiotensin II (Ang II) in pulmonary vein endothelial cells (PVEC). Since Pyk2 has no calcium binding domain, and neither Ca(2+) nor Ca(2+)/calmodulin directly activates Pyk2, it is not clear how Ca(2+) transduces the signal to activate Pyk2, a key tyrosine kinase, in the early events of Ang II signaling. In the present study, we investigated the mechanism of the calcium-dependent activation of Pyk2 in response to Ang II by using 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors and isoprenoid intermediates in PVEC. We have obtained substantial evidence indicating that Ang II activates Pyk2 through calcium-mediated activation of the geranylgeranylated small G protein Rap1 and the Rap1 association with Pyk2. Thus, the small G protein Rap1 is an intermediary signaling molecule linking Ang II-induced calcium signal to Pyk2 activation in PVEC. In addition, our results indicate that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, a class of cholesterol-lowering drugs, could interrupt Ang II signaling independent of cholesterol lowering in endothelial cells.

Angiotensin II↗
PubMed2001

Assembly of the 26S proteasome is regulated by phosphorylation of the p45/Rpt6 ATPase subunit.

We investigated whether the assembly/disassembly of the 26S proteasome is regulated by phosphorylation/dephosphorylation. The regulatory complex disassembled from the 26S proteasome was capable of phosphorylating the p45/Sug1/Rpt6 subunit, suggesting that the protein kinase is activated upon dissociation of the 26S proteasome or that the phosphorylation site of p45 becomes susceptible to the protein kinase. In addition, the p45-phosphorylated regulatory complex was found to be incorporated into the 26S proteasome. When the 26S proteasome was treated with alkaline phosphatase, it was dissociated into the 20S proteasome and the regulatory complex. Furthermore, the p45 subunit and the C3/alpha2 subunit were cross-linked with DTBP, whereas these subunits were not cross-linked by dephosphorylating the 26S proteasome. These results indicate that the 26S proteasome is disassembled into the constituent subcomplexes by dephosphorylation and that it is assembled by phosphorylation of p45 by a protein kinase, which is tightly associated with the regulatory complex. It was also revealed that the p45 subunit is directly associated with the 20S proteasome alpha-subunit C3 in a phosphorylation-dependent manner.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2001

Neurogenic bladder in Lambert-Eaton myasthenic syndrome and its response to 3,4-diaminopyridine.

Autonomic dysfunction, as well as neuromuscular involvement, is a common manifestation of Lambert-Eaton myasthenic syndrome (LEMS). Dry mouth and impotence have been described as typical features of autonomic dysfunction, but neurogenic bladder is infrequent or subclinical in LEMS. We report a patient with neurogenic bladder secondary to LEMS whose condition responded to 3,4-diaminopyridine (3,4-DAP). In this patient's serum, results of repeated measurement with P/Q-type VGCC antibodies proved positive, but not with N-type VGCC and synaptotagmin antibodies. A review of the literature turned up a few patients with voiding dysfunction related to LEMS, but no urodynamic studies were done on these patients. Ours is the first case in which 3,4-DAP was efficacious in treating LEMS and neurogenic bladder. Responses of 3,4-DAP in urodynamic studies suggest that in this LEMS patient neurogenic bladder was caused by defective neurotransmission both in the autonomic detrusor and skeletal abdominal muscles.

4-Aminopyridine↗
PubMed2001

Rhodocytin induces platelet aggregation by interacting with glycoprotein Ia/IIa (GPIa/IIa, Integrin alpha 2beta 1). Involvement of GPIa/IIa-associated src and protein tyrosine phosphorylation.

Although glycoprotein Ia/IIa (GPIa/IIa, integrin alpha(2)beta(1)) has established its role as a collagen receptor, it remains unclear whether GPIa/IIa mediates activation signals. In this study, we show that rhodocytin, purified from the Calloselasma rhodostoma venom, induces platelet aggregation, which can be blocked by anti-GPIa monoclonal antibodies. Studies with rhodocytin-coupled beads and liposomes loaded with recombinant GPIa/IIa demonstrated that rhodocytin directly binds to GPIa/IIa independently of divalent cations. In vitro kinase assays and Western blotting of GPIa immunoprecipitates revealed that Src and Lyn constitutively associate with GPIa/IIa and that Src activity increases transiently after rhodocytin stimulation. Src specifically associates with p130 Crk-associated substrate (Cas) in a manner dependent upon Cas phosphorylation, suggesting that Src is responsible for Cas tyrosine phosphorylation. While all these phenomena occur early after rhodocytin stimulation in a cAMP-resistant manner, tyrosine phosphorylation of Syk and phospholipase Cgamma2, intracellular Ca(2+) mobilization, and platelet aggregation occur later in a cAMP-sensitive manner. Cytochalasin D, which interferes with actin polymerization and blocks receptor clustering, inhibits all the rhodocytin-mediated signals we examined in this study. We suggest that rhodocytin, by clustering GPIa/IIa, activates GPIa/IIa-associated Src, which then mediates downstream activation signals.

Animals↗
PubMed2001

An improved sodium dodecyl sulfate-polyacrylamide gel electrophoresis system for the analysis of membrane protein complexes.

Membrane protein complexes such as the reaction center complexes of oxygenic photosynthesis or the complex I of mitochondira are composed of many subunit polypeptides. To analyze their polypeptide compositions by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), a wide range of molecular sizes has to be resolved, especially in the low molecular mass range. We have improved the traditional Tris/HCI buffer systems adopting a Tris/2-(N-morpholino)ethanesulfonic acid (MES) buffer system containing 6 M urea. This gel system was used with an 18-24% acrylamide gradient for the separation of polypeptides with molecular masses from below 5 kDa to over 100 kDa. This buffer system can also be applied to the usual uniform concentration of acrylamide gel and also to minislab gels.

Acrylic Resins↗
PubMed2001

Involvement of ErbB-2 in rheumatoid synovial cell growth.

OBJECTIVE: The synovial tissue affected by rheumatoid arthritis (RA) is characterized by hyperproliferation of synovial cells. High amounts of epidermal growth factor (EGF) in the synovial fluid of RA patients contribute to the growth of rheumatoid synovial cells. To characterize the receptor for EGF in rheumatoid synovial cells, the expression and function of ErbB family members were examined. METHODS: Synovial tissues were obtained from surgical excisions. The expression of ErbB products was examined by immunohistochemistry and immunoblotting by using specific antibodies. Primary cultures were established from the surgical materials. Cell growth was measured using MTT. The levels and phosphorylation state of the ErbB-2 protein were analyzed by immunoprecipitation and immunoblotting. RESULTS: The expression of ErbB-2, but not other ErbB-related products, was detected in synovium with RA as compared with that with osteoarthritis (OA) and ligament injury. Growth of primary synovial cells with RA was inhibited by genistein, a tyrosine kinase inhibitor, and herceptin, a specific monoclonal antibody against ErbB-2. Herceptin showed a small effect on growth of primary synovial cells with OA. EGF stimulated the phosphorylation of ErbB-2 in primary synovial cells with RA. This EGF-stimulated phosphorylation was completely abrogated by genistein and herceptin. CONCLUSION: ErbB-2 is expressed in rheumatoid synovial cells and may function as the receptor for EGF. Our data suggest that mitotic signals from EGF family members are transduced by ErbB-2 in these cells. Inhibition of ErbB-2 may provide a new approach to the effective treatment for RA.

Adult↗
PubMed2001

Effects of Dai-kenchu-to, a herbal medicine, on uterine and intestinal motility.

The effects of both Dai-kenchu-to and PGF(2alpha) on intestinal and uterine motility were studied in anaesthetized rabbits with force transducers implanted in the jejunum, ileum and uterus. A single intraduodenal administration of Dai-kenchu-to (300 mg/kg) enhanced the intestinal motility but not the uterine motility. However, intravenous administration of PGF(2alpha) (20 microg/kg) enhanced both intestinal and uterine motility. The effects of Dai-kenchu-to on the spontaneous contraction and contractile response of the isolated rat uterine strips to oxytocin, PGF(2alpha) or ACh were also studied. Oral administration of Dai-kenchu-to at 300 mg/kg for one week had no effect on either the spontaneous contraction or the contractile response of the uterus. These results indicate that Dai-kenchu-to may exert stimulatory effects on intestinal motility, as PGF(2alpha), but has no effect on the uterine motility, suggesting a selective effect on the gastrointestinal tract. Hence, Dai-kenchu-to may be safer than PGF(2alpha) in the treatment of postoperative adhesive ileus in women. However, more studies are needed to determine whether Dai-kenchu-to could be administered to pregnant women.

Animals↗
PubMed2001

Biological activity of kiwifruit peel extracts.

Various bioactive substances in kiwifruit extracts were fractionated by organic solvent extractions, followed by silica gel and ODS chromatographies. Both cytotoxic activity and multi-drug resistance reversal activity were found in the less polar fractions. Cytotoxic activity was not always parallel the radical intensity. Antibacterial activity was distributed into various fractions and all fractions were inactive against Candida albicans and H. pylori. Only 70% methanol extracts showed anti-human immunodeficiency virus activity, and produced a broad ESR signal under alkaline conditions, in a fashion similar to lignin. These fractions also effectively scavenged O(2)(-) produced by the xanthine-xanthine oxidase reaction, suggesting a bimodal (pro-oxidant and antioxidant) action. These data suggest a medicinal efficacy of kiwifruit peel extracts.

Animals↗
PubMed2001

99mTc-MIBI SPECT in small cell lung cancer patients before chemotherapy and after unresponsive chemotherapy.

We evaluated the accumulation of 99mTc-MIBI in small cell lung cancer patients before chemotherapy and after unresponsive chemotherapy. The pre-chemotherapeutic group included 22 newly diagnosed patients. These patients underwent a 99mTc-MIBI SPECT study before starting chemotherapy. After chemotherapy, based on changes in tumor size, three different patterns of response (complete remission: CR, partial remission: PR and no change: NC) were defined. The post-chemotherapeutic group included 11 patients after chemotherapy who did not respond to chemotherapy. These patients underwent a 99mTc-MIBI SPECT study after completion of chemotherapy. SPECT images were acquired 15 min (early) and 2 hr (delayed) after injection of 99mTc-MIBI. With a region of interest technique, the early ratio, delayed ratio and retention index were calculated. Early and delayed ratios in pre-chemotherapeutic patients were significantly higher than those in post-chemotherapeutic patients. There were no significant differences between the pre-chemotherapeutic and post-chemotherapeutic patients in the retention index. In the pre-chemotherapeutic patients, early and delayed ratios for the CR and PR groups were significantly higher than those for the NC group. There were no significant differences in the retention index with respect to the tumor response. 99mTc-MIBI might be useful for evaluating the tumor chemosensitivity in patients with small cell lung cancer.

Adult↗
PubMed2001

Guglielmi detachable coil embolization for ruptured lower-midbasilar trunk aneurysms--a report of five cases.

Detachable coil embolization currently plays an essential role for patients with ruptured basilar artery aneurysms, even though it may have an unfavorable outcome and there may be some technical problems of embolization. We describe Guglielmi detachable coil (GDC) embolization for five ruptured lower-mid basilar trunk aneurysms, using a variety of techniques. The patients' ages ranged from 61 to 78 years; Hunt and Kosnik grade was distributed from 2 to 4, and three patients were found to have fenestrations of the lower basilar arteries. All patients underwent aneurysmal embolization at the subacute or chronic stage. The transfemoral route was used in three patients--one of whom, with a wide-necked aneurysm, was treated by the balloon remodeling technique. The transbrachial approach was chosen for the fourth patient, while vertebral artery origin exposure followed by a direct puncture was achieved in the fifth. All patients were assessed with 80-100% aneurysmal obliteration. No patient re-bled after the embolization. Small cerebellar infarction, possibly due to embolism from the obliterated aneurysmal sac, occurred 11 days after the treatment. Of the five patients, four achieved a good recovery, and one became severely disabled. Ruptured basilar trunk aneurysms can be successfully treated with GDC embolization. In addition to the routine transfemoral route, the transbrachial route, direct vertebral artery puncture, and balloon remodeling technique are also useful for the embolization of this location of aneurysm.

Aged↗
PubMed2001

Comparative evaluation of 99mTc-MIBI and 99mTc-HMDP scintimammography for the diagnosis of breast cancer and its axillary metastases.

The purpose of the present study was to compare scintimammography using technetium-99m hexakis 2-methoxyisobutylisonitrile (MIBI) with that using 99mTc-hydroxymethylene diphosphonate (HMDP) in the detection of breast cancer and its axillary lesions. The study population comprised 50 consecutive females with breast cancer who were scheduled for surgery. All patients underwent scintimammography with 99mTc-MIBI and 99mTc-HMDP. The images were acquired 5 min (early) and 2 h (delayed) after injection of each radiopharmaceutical. Regions of interest were placed over the breast tumour (T), the axillary lesion (A) and the normal ipsilateral breast tissue (N). The two count ratios were calculated, i.e. the tumour to normal breast tissue ratio (T/N) and the axillary lymph node to normal breast tissue ratio (A/N). For the breast tumours, using 99mTc-MIBI the positive rate was 86% (43/50) for the early and 72% (36/50) for the delayed images. The corresponding values using 99mTc-HMDP were 72% (36/50) and 40% (20/50), respectively. Histopathological examination revealed metastatic lymph node involvement in 22 patients. For the axillary lesions, using 99mTc-MIBI the positive rate was 72.7% (16/22) for the early and 54.5% (12/22) for the delayed images. Using 99mTc-HMDP, the positive rate was only 18.2% (4/22) for the early and 4.5% (1/22) for the delayed images. Using 99mTc-MIBI, the mean T/N (+/- SD) ratios on early and delayed images were 2.69 +/- 1.64 and 2.03 +/- 1.16, respectively, and the mean A/N (+/- SD) ratios on early and delayed images were 2.20 +/- 1.23 and 1.80 +/- 1.20, respectively. The corresponding values using 99mTc-HMDP were 1.77 +/- 0.91, 1.42 +/- 0.72, 1.27 +/- 0.63 and 1.08 +/- 0.25, respectively. The T/N and A/N ratios on the early and delayed 99mTc-MIBI images were both significantly higher than those obtained using 99mTc-HMDP. 99mTc-MIBI scintimammography is more sensitive than 99mTc-HMDP scintimammography for the detection of breast cancer and its axillary lymph node metastases.

Adult↗
PubMed2001

Replacement of the canine inferior vena cava with a seeded graft.

The patency and microscopic findings of gelatin-coated Dacron grafts seeded with endothelial cells and implanted into the inferior vena cava of dogs was evaluated. A total of 25 mongrel dogs were divided into four experimental groups according to whether or not an antiplatelet agent was administered and a seeded or nonseeded graft was implanted. In the groups not given antiplatelet therapy that were implanted with a nonseeded graft, occlusion of the graft occurred soon after surgery. In contrast, in the majority of animals implanted with a seeded graft and given antiplatelet therapy, graft patency was evident for up to 4 weeks postoperatively. In the latter animals, scanning electron microscopy 4 weeks after surgery showed the formation of confluent endothelial-like cells within 5 mm from the anastomosis, as well as insular endothelial-like cells in the central part of the graft. The simple centrifugal seeding method enables endothelial-like cells to adhere to grafts, suggesting that it may be useful in venous replacement.

Animals↗
PubMed2001

Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia.

Pseudohypoparathyroidism Ia (PHP-Ia), is an inherited disease with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the phenotype of Albright hereditary osteodystrophy (AHO), including short stature, obesity, round face, brachydactyly, and subcutaneous ossification. This disease is caused by mutation that inactivates the alpha-subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the Gsalpha gene were identified in two Japanese patients with sporadic PHP-Ia. Deletion of a G in exon 4 at codon 88 in the first patient produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amino acid is located in a region, switch 2, that is thought to interact with the betagamma subunit of Gsalpha protein, this mutation may impair Gs protein function. We report here one novel Gsalpha mutation, and note that mutations in Japanese patients with PHP-Ia are probably heterogeneous.

Adult↗
PubMed2001

Cisplatin inhibits the expression of X-chromosome-linked inhibitor of apoptosis protein in an oral carcinoma cell line.

Cisplatin is known to activate caspase-3 through the mitogen-activated kinase (MAPK) pathway. We found that X-chromosome-linked inhibitor of apoptosis protein (XIAP), a direct inhibitor of caspase-3, 7, and 9, is constitutively expressed in a cell line of oral squamous cell carcinoma, KOSC-2. Cisplatin treatment of the cells inhibited the expression of XIAP, and this was associated with DNA fragmentation. Overexpression of XIAP, by a transfection experiment, inhibited the cisplatin-induced apoptosis. We conclude that cisplatin induces apoptosis mediated not only by the activation of MAPK pathway but by the inhibition of XIAP.

Antineoplastic Agents↗
PubMed2001

Ruptured epidermoid cyst and haematoma of spleen: a diagnostic clue of high levels of serum carcinoembryonic antigen, carbohydrate antigen 19-9 and Sialyl Lewis x.

Splenic epidermoid cyst is a rare disease and that with haematoma is even more rare. The case of epidermoid cyst of the spleen is described, in a 36-year-old Japanese female, manifesting as left hypochondralgia and rupture of the cyst. Clinical features were splenic lesion 14 cm in diameter and consisting of round-hypovascular and crescent-hypervascular sublesions. Extravasation of cystic fluid was detected in abdominal cavity Preoperative diagnosis was difficult due to such uncommon features, however high levels of serum tumour markers (carcinoembryonic antigen, carbohydrate antigen 19-9, Sialyl Lewis x) strongly suggested epidermoid cyst. Laparotomic splenectomy and cholecystectomy were performed for splenic lesion and gallstones, and serum tumour markers decreased following surgery. Pathological diagnosis of the round-hypovascular lesion was epidermoid cyst and crescent-hypervascular lesion was haemorrhage (haematoma).

Adult↗
PubMed2001

Mechanisms for contractile effect of Dai-kenchu-to in isolated guinea pig ileum.

The mechanisms by which Dai-kenchu-to (TJ-100), a kampo medicine, enhances gastrointestinal motility was investigated using isolated guinea pig ileum. TJ-100 induced contractions accompanied by autonomous contraction at a concentration of more than 3 x 10(-4) g/ml in a dose-related manner. The TJ-100-induced ileal contraction was suppressed by atropine and tetrodotoxin, but not by hexamethonium. This effect was partially suppressed in the presence of high concentrations of ICS 205-930, a serotonin 4 (5-HT4) receptor antagonist. In addition, TJ-100 showed an acetylcholine (ACh)-releasing action in the smooth muscle tissues of ileum. These results suggest that contractile response induced by TJ-100 is partially mediated by ACh released from the cholinergic nerve endings and that 5-HT4 receptors would be involved in the effect of TJ-100.

Acetylcholine↗