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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 109 records · Page 6Linked to original sources

Lysophosphatidylcholine activates transcription factor NF-kappaB and AP-1 in AR42J cells.

Phospholipase A2 (PLA2) has been suggested in the pathogenesis of acute pancreatitis, in part through the PLA2-generated phospholipid by-products, most notably lysophosphatidylcholine (lyso-PC). The effects of lyso-PC on pancreatic acinar cells other than necrosis are poorly characterized. Recent studies have suggested a role of the activation of transcription factors such as nuclear factor kappa B (NF-kappaB) for the pathogenesis of acute pancreatitis. Here we examined the effects of lyso-PC on the activation of transcriptional factors in rat pancreatic AR42J cells. Lyso-PC induced apoptosis at concentrations > or = 10 microM. At 10 and 25 microM, lyso-PC increased the NF-kappaB- and activator protein-1 (AP-1)-specific DNA binding activity as determined by electrophoretic mobility shift assay. Lyso-PC also increased the transcriptional activity of NF-kappaB and AP-1 as assessed by luciferase assay. Lyso-PC increased the mRNA level of pancreatitis-associated protein-I and c-jun. Lyso-PC activated three classes of mitogen activated protein kinases: extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase/stress-activated protein kinase and p38 kinases. Activation of transcription factors by lyso-PC was not altered by a specific platelet activating factor receptor antagonist, TCV-309, suggesting that the activation was independent of the platelet activating factor receptor. These molecular events may suggest a novel role of lyso-PC for the modulation of acinar cell function.

Acute Disease↗

Analysis of immunoglobulin secretion by lymph organs with myasthenia gravis.

OBJECTIVES: To investigate in vitro anti-acetylcholine receptor (AChR) antibody secretion by lymph organs with myasthenia gravis (MG) with special attention to clinical status and stages. MATERIALS AND METHODS: Twenty MG patients before therapy were included in this study. Four patients were negative for serum anti-AChR antibodies (AChRAb). All patients received extended thymectomy. Thymic cells, bone marrow (BM) cells and peripheral blood mononuclear cells (PBMC) were cultured for 1 week. AChRAb secretion and IgG secretion in the culture medium were determined by immunoprecipitation assays and ELISA respectively. RESULTS: PBMC secreted AChRAb and IgG most efficiently, followed by BM cells, and then thymic cells. Even in patients whose diseases were of short duration (less than 2 months), the tendency was not changed. AChRAb secretion by BM cells and PBMC significantly correlated with serum AChRAb levels. Thymectomy did not change AChRAb or IgG secretion by PBMC within 3 months. AChRAb secretion by PBMC paralleled the clinical status. Some seronegative patients turned positive by culturing PBMC. CONCLUSION: PBMC is the most efficient site at producing AChRAb, even in patients of short duration (equal to, or less than, 2 months). Monitoring AChRAb secretion by PBMC is useful to estimate the autoimmune activity of MG.

Adolescent↗

Epidemiology of suicidal ideation and help-seeking behaviors among the elderly in Japan.

This study offers an analysis of the elderly (over 65 years of age) among a general community population in terms of the percentages of: (i) persons with recurring thoughts of death and/or of committing suicide, and (ii) people who have consulted others, including medical professionals, with regard to these problems. Among 433 elderly over the age of 65 in one community in a town in Aomori Prefecture, 358 agreed to participate in the project. Forty-four participants (12.3%) responded that they had either 'thoughts of death' or 'thoughts of suicide', and these thoughts had continued for more than 2 weeks in 12 participants (3.4%). Only 15 of the 44 suicidal elderly responded that they had consulted someone about their problems. Although there are many elderly people exhibiting a subclinical depressive state with recurring thoughts of death or thoughts of suicide, the number of people who consult family members, professionals, or others is very low. This suggests the importance of community networking through educational activities so that people can more readily talk to and support one another.

Aged↗

p53 expression in the gastric mucosa before and after eradication of Helicobacter pylori.

BACKGROUND: Accumulation of p53 has been recognized in the gastric mucosa infected with Helicobacter pylori. We investigated the prevalence of p53-positive cells in the gastric mucosa before and one month after eradication of H. pylori and the relationship between p53 positivity and inflammation and cell proliferation. METHODS: The subjects included 24 H. pylori-positive patients. They achieved eradication one month after anti-H. pylori therapy. Biopsies were taken from the greater curvatures of the antrum and middle body. H. pylori status was assessed using culture and tissue section (Giemsa stain). Serial sections were used for examination of gastritis (hematoxylin and eosin stain) and for immunostaining of p53, Ki-67 and myeloperoxidase (MPO). p53 index and Ki-67 labeling index (LI) were calculated by counting p53-positive and Ki-67-positive cells in the entire gastric pits longitudinally sectioned and expressing them as a percentage of the total cells in a gastric pit. In the neck regions with and without p53-positive cells, polymorphonuclear leukocytes (PMNs) were counted in the corresponding area (/50 x 50 microm2) of the sections stained both with p53 and MPO. RESULTS: p53-positive cells decreased significantly after eradication of H. pylori. Before eradication, the number of PMNs was significantly higher in the neck regions with p53-positive cells than in those without. CONCLUSIONS: In the gastric mucosa infected with H. pylori, p53-positive cells were found in the neck region infiltrated with PMNs. p53 expression decreased significantly one month after eradication of H. pylori.

Adult↗

Guidelines in the management of Helicobacter pylori infection in Japan.

BACKGROUND: In preparation of the approval of Helicobacter pylori therapy by the Japanese national health system, the board of directors of the Japanese Society for Helicobacter Research decided to prepare guidelines on the diagnosis and treatment of H. pylori infection for physicians in routine medical practice. METHODS: A guidelines preparation committee was formed and six meetings were held. Then, in December 1999, a consensus meeting was held in Kobe to obtain the opinions of general practitioners as well as experts from Europe, North America, and Asia. RESULTS: Helicobacter pylori eradication therapy is recommended in gastric or duodenal ulcer patients. Helicobacter pylori eradication therapy is recommended or gastric mucosa associated lymphoid tissue (MALT) lymphoma but it should be done at specialist institutions. The significance of H. pylori eradication therapy is still under evaluation in patients with hyperplastic polyps, chronic atrophic gastritis, non-ulcer dyspepsia and in patients after endoscopic mucosal resection of gastric cancer and after gastrectomy for gastric cancer. When diagnosing H. pylori infection, at least one of the tests requiring endoscopic biopsy (e.g. rapid urease test, histology, or culture) and tests not requiring biopsy (e.g. measurement of H. pylori antibody or urea breath test) should be used. Multiple tests are recommended to increase the accuracy. The drugs of first choice currently covered by the national health insurance system in Japan are: lansoprazole (30 mg) 1 capsule twice daily, amoxicillin (250 mg) 3 capsules twice daily, and clarithromycin (200 mg) 1-2 tablets twice daily. These three drugs should be administered after breakfast and dinner for 1 week. CONCLUSION: These guidelines are intended for utilization in routine medical practice after the Japanese national health system begins to cover the management of H. pylori infection.

Amoxicillin↗

A multicenter, double-blind study on triple therapy with lansoprazole, amoxicillin and clarithromycin for eradication of Helicobacter pylori in Japanese peptic ulcer patients.

BACKGROUND: Two triple therapies with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of Helicobacter pylori were studied in multicenter, double-blind fashion to evaluate the eradication rate of H. pylori and safety of eradiation treatment in Japanese patients with H. pylori-positive active gastric ulcers or duodenal ulcers. METHODS: Patients were randomly chosen for the control treatment of LPZ 30 mg twice a day (b.i.d.; Group A-LPZ-only) or the test treatments of LPZ 30 mg plus AMPC 750 mg and CAM 200 mg b.i.d. (Group B-LAC200) and LPZ 30 mg, AMPC 750 mg and CAM 400 mg b.i.d. (Group C-LAC400). All eradication treatments lasted for a period of 7 days. Successful eradication was assessed by culture and gastric histology 1 month after completion of the ulcer treatment. RESULTS: The eradication rates of H. pylori in the full analysis set were 0% in Group A-LPZ-only, 87.5% in Group B-LAC200 and 89.2% in Group C-LAC400 for gastric ulcer and, 4.4% in Group A-LPZ-only, 91.1% in Group B-LAC200 and 83.7% in Group C-LAC400 for duodenal ulcer. The eradication rates of Group B-LAC200 and Group C-LAC400 were 89.2% (95% CI: 84.8-93.7%) and 86.4% (95%CI: 81.5-91.3%) in total in the full analysis set, 89% (95% CI: 84.3-93.7%) and 85.3% (95%CI: 80.1-90.5%) in the per protocol set. The eradication rates in Groups B-LAC200 and group C-LAC400 were statistically significantly higher than the rate in Group A-LPZ-only for both gastric ulcer and duodenal ulcer patients (p <.0001 for both). CONCLUSION: A satisfactorily high H. pylori eradication rate was obtained in Japanese ulcer patients with the triple therapy regimen consisting of LPZ 30 mg, AMPC 750 mg, and CAM 200 mg b.i.d.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Direct superoxide scavenging activity of nonsteroidal anti-inflammatory drugs: determination by electron spin resonance using the spin trap method.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which are used widely to manage pain, are known to inhibit cyclooxygenase, but details of the mechanisms of NSAID action remain unclear. We investigated the ability of three NSAIDs (indomethacin, loxoprofen, and etodolac) to eliminate and inhibit free radicals. Superoxide scavenging activity of these NSAIDs was measured in vitro by electron spin resonance spectrometry using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as a spin trap. Electron spin resonance demonstrated that formation of superoxide-DMPO spin adduct was completely inhibited by two nonselective cyclooxygenase inhibitors, indomethacin (3 mmol) and loxoprofen (3 mmol). The electron spin resonance study also demonstrated that the formation of superoxide-DMPO spin adduct was strongly inhibited by a selective cyclooxygenase-2 inhibitor, etodolac, in a concentration-dependent manner. These results indicate that NSAIDs, including indomethacin, loxoprofen, and etodolac, have direct superoxide scavenging activity.

Anti-Inflammatory Agents, Non-Steroidal↗

Location and length of arteriovenous fistulas around axial-pattern skin-flap pedicles.

The importance of the location of a surgically-created arteriovenous fistula around the pedicle (both distal and proximal) on the viability of rat skin flaps was investigated. The animals were randomly divided into four groups. Group 1 included bilateral standard island groin flaps. The right side flap was used as a control. On the left side, after elevation of the flap, an X-type arteriovenous fistula greater than 1 mm (up to 2 mm) in length was created distal to the pedicle, and just before the bifurcation of the common femoral vessels. In Group 2, the flap was an axial-pattern medially-based peninsular flap, including the same vessels. In this group also, two flaps were elevated bilaterally, and the right side was used as a control; on the left side, an X-type arteriovenous fistula the same length as in Group 1 was also created distal to the pedicle. In both groups, all other branches of the common femoral vessels were kept intact. In a second part of the study, two other animal groups were used to clarify the importance of the length of the arteriovenous fistula on the viability of skin flaps. In Group 3, the model was the same as in Group 1, but the fistula was 1 mm in length. In Group 4, the length of the fistula was 1 mm, and its location was on the common femoral vessels proximal to the pedicle, using the same flap model. Flow values were measured repeatedly using a laser Doppler flowmeter. Histopathologic studies were also done. There are three important points arising from these studies. 1). The location of an X-type arteriovenous fistula around an island skin flap pedicle seems to be more important than diameter. An arteriovenous fistula proximal to the pedicle is more hazardous than an arteriovenous fistula distal to the pedicle, regarding island skin-flap viability. 2). However, the length of the fistula is also important, and an arteriovenous fistula distal to the pedicle, with a sufficiently long length, is not devoid of harmful effects. It is also clear that the larger the fistula, the greater the systemic effects. 3). An island skin flap with an arteriovenous fistula distal to its pedicle might be a useful model to study the relationship between skin-flap viability and edema formation.

Anastomosis, Surgical↗

Analyses of muscular activity, energy metabolism, and muscle fiber type composition in a patient with bilateral masseteric hypertrophy.

Hyperwork of the masseter muscles due to habitual parafunction is thought to induce masseteric hypertrophy (so called work hypertrophy). However, the causes underlying this disease are not yet fully understood. Recently, we had a patient with bilateral masseteric hypertrophy, and we performed a partial excision of the masseter muscles. In this patient's case, we examined muscular activity, energy metabolism, and fiber type composition of the masseter muscles using electromyograms (EMG), 31P-magnetic resonance spectroscopy (MRS), and enzyme-histochemistry. The EMG showed no hyperactivity, and the 31P-MRS showed normal energy spectral patterns and PCr contents of the masseter muscles. The fiber type composition, however, in the muscles in this case was very different from that in muscles with "work hypertrophy" and also that in normal masseter muscles: 1. Loss of type IIB fibers; 2. Increases in type IIA and in type IM & IIC fibers; and 3. Decrease in type I fibers. The findings suggest that this is not a case of work hypertrophy but a case of compensatory hypertrophy possibly due to a lack of high-tetanus-tension type IIB fibers.

Adenosine Triphosphate↗

Radical production and cytotoxic activity of tert-butyl-substituted phenols.

2,4,6-Tri-tert-butylphenol (TBP)-related compounds are used for stabilizing plastics by making them resistant to oxidation. However, the cytotoxic activity of these compounds has not yet been established. TBP produced phenoxyl radicals at pH >or= 9.0 and 2,4-di-t-butylphenol (DBP) at pH 12.5, but 3,3',5,5'-tetra-t-butyl-1,1'-biphenyl-2,2'-diol (bisDBP) did not, using ESR spectroscopy. Both superoxide anion radical (O(2)(-)) scavenging activity and reactive oxygen species (ROS) production activity declined in the order of TBP > DBP > bisDBP. The cytotoxic activity against human oral tumor cell lines (HSC-2, HSG) and human gingival fibroblast cells (HGF) declined in the order of DBP >> bisDBP = TBP = TBP-OOH (2,4,6-tri-t-butyl-4-hydroperoxy-2,5-cyclohexadiene-1-one). The cytotoxic activity of TBP, but not of DBP or bisDBP was significantly enhanced after visible light (VL)-irradiation for 10 min. The cytotoxicity of irradiated TBP was significantly higher than that of either original TBP or TBP-OOH, the oxidative metabolite of TBP, possibly due to the formation of TBP stable radical and ROS via oxidation. In contrast, the cytotoxic activity of DBP and bisDBP was independent of radical production, and therefore, may be intrinsic. A non-enzymatic oxidation decomposition of DBP or TBP was estimated from the formation of reaction enthalpy (DeltaH) using a modified neglect of diatomic overlap, parametric method 3 (MNDO-PM3) semi-empirical method, suggesting that O(2) is capable of activating DBP to a reactive quinone or dimer and that TBP phenoxyl radicals via oxidation directly affect extra- or intracellular bioactive materials, resulting in the induction of cytotoxicity.

Antioxidants↗

Interactions among a fimbrin, a capping protein, and an actin-depolymerizing factor in organization of the fission yeast actin cytoskeleton.

We report studies of the fission yeast fimbrin-like protein Fim1, which contains two EF-hand domains and two actin-binding domains (ABD1 and ABD2). Fim1 is a component of both F-actin patches and the F-actin ring, but not of F-actin cables. Fim1 cross-links F-actin in vitro, but a Fim1 protein lacking either EF-hand domains (Fim1A12) or both the EF-hand domains and ABD1 (Fim1A2) has no actin cross-linking activity. Overexpression of Fim1 induced the formation of F-actin patches throughout the cell cortex, whereas the F-actin patches disappear in cells overexpressing Fim1A12 or Fim1A2. Thus, the actin cross-linking activity of Fim1 is probably important for the formation of F-actin patches. The overexpression of Fim1 also excluded the actin-depolymerizing factor Adf1 from the F-actin patches and inhibited the turnover of actin in these structures. Thus, Fim1 may function in stabilizing the F-actin patches. We also isolated the gene encoding Acp1, a subunit of the heterodimeric F-actin capping protein. fim1 acp1 double null cells showed more severe defects in the organization of the actin cytoskeleton than those seen in each single mutant. Thus, Fim1 and Acp1 may function in a similar manner in the organization of the actin cytoskeleton. Finally, genetic studies suggested that Fim1 may function in cytokinesis in cooperation with Cdc15 (PSTPIP) and Rng2 (IQGAP), respectively.

Actin Depolymerizing Factors↗

Oxidative stress promotes the development of transformation: involvement of a potent mutagenic lipid peroxidation product, acrolein.

The effect of intracellular oxidative stress on the development of cell transformation was studied. Mouse embryo C3H/10T1/2 fibroblasts pre-treated with benzo[a] pyrene, developed transformed foci on exposure to free radical generators, such as 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and 3-morpholinosydnonimine hydrochloride (SIN-1). These compounds generate peroxyl radicals and peroxynitrite, respectively. Neither AAPH nor SIN-1 alone induced transformation. The level of intracellular antioxidants, such as alpha-tocopherol and glutathione (GSH), decreased with time of exposure to the free radical generators, whereas the addition of exogenous alpha-tocopherol, GSH and ebselen showed a reduction in the frequency of transformation. An early event during exposure to AAPH and SIN-1 was the generation of acrolein, a highly mutagenic lipid peroxidation product, which was suppressed by the addition of alpha-tocopherol. Furthermore, it was confirmed that acrolein induced the transformation of cells which were pre-treated with benzo[a]pyrene but not of the untreated cells. These results suggest that acrolein may act as an important mediator of cell transformation under oxidative stress.

Acrolein↗

Binding diversity of a noncovalent-type low-molecular-weight serine protease inhibitor and function of a catalytic water molecule: X-ray crystal structure of PKSI-527--inhibited trypsin.

PKSI-527 is a noncovalent-type low-molecular-weight inhibitor. The X-ray crystal structure of the trypsin-PKSI-527 complex revealed a binding mode (Form II) different from the previously reported one (Form I) [Nakamura, M. et al. (1995) Biochem. Biophys. Res. Commun. 213, 583--587]. In contrast to the previous case, the electron density of the inhibitor revealed the whole structure clearly. Each structural part of the inhibitor in Forms I and II was differently located at the active site, although the modes of binding of the terminal amino group to the Asp189 carboxyl group were similar. This binding diversity, which is a characteristic of the noncovalent-type low-molecular-weight inhibitor, provides a suitable example for estimating the possible mechanism toward the enzymatic inhibition, together with the structural basis necessary for a specific inhibitor. The mode of binding in Form II reflects the inhibitor-specific situation and is in contrast with the substrate-mimetic binding mode for Form I. Based on the generally accepted catalytic mechanism for serine protease, we propose that a water molecule located at the catalytic site plays an important role in blocking the catalytic function of the reactive Ser193 OH group.

Animals↗

The establishment of conditions to efficiently screen photosynthesis-deficient mutants of Synechocystis sp. PCC 6803 by nitrofurantoin treatment.

A method based on the susceptibility of photosynthetic organisms to nitrofurantoin under illumination was established to screen mutants of Synechocystis sp. PCC 6803 deficient in the function of photosystem II, which were created by random PCR mutagenesis targeted to the psbAII gene coding for the D1 protein of the photosystem II reaction center. In this method, cyanobacterial colonies on a nitrocellulose membrane on a BG11 agar plate were treated with nitrofurantoin at 1.0 mM under white light at 40 microE x m(-2 ) x s(-1) for 2 h, and then kept under normal conditions without nitrofurantoin so that surviving cells could grow. This method was also shown to be useful for screening mutants deficient in the function of photosystem I.

Cyanobacteria↗

Isolation and characterization of oxygen-evolving thylakoid membranes and photosystem II particles from a glaucocystophyte, Cyanophora paradoxa.

Conditions for preparing oxygen-evolving thylakoid membranes and PSII complexes, and those for observing the PSII activity were investigated in a glaucocystophyte, Cyanophora paradoxa. The active thylakoid membranes were isolated either with a medium containing glycerol or with that containing high concentrations of sucrose, phosphate, and citrate. Active PSII particles were solubilized by octyl-beta-D-glucoside from thylakoid membranes and were separated by sucrose density gradient centrifugation. The thylakoid membranes and PSII particles showed an oxygen-evolving activity only in high-ionic-strength media. The extrinsic 33 kDa protein (PsbO) and the cytochrome c(550) (PsbV) were found to be present in the PSII particles as in cyanobacteria or red algae, but no 12 kDa protein (PsbU) was detected. The PsbO protein was classified as a land-plant type by its N-terminal amino acid sequence.

Absorptiometry, Photon↗

Acclimation to the growth temperature and the high-temperature effects on photosystem II and plasma membranes in a mesophilic cyanobacterium, Synechocystis sp. PCC6803.

High-temperature effects on Photosystem II and plasma membranes, temperature dependence of growth, and acclimation to the growth temperature were studied in a mesophilic cyanobacterium, Synechocystis sp. PCC6803. The following results were obtained. (1) Small but distinct temperature acclimation of the PSII reaction center activity was shown for the first time when the activity was measured at inhibitory high temperatures. However, the reaction center activity showed no apparent acclimation when it was measured at growth temperatures after heat stress. (2) Oxygen-evolving activity and the permeability of plasma membranes showed higher resistance to heat when PCC6803 cells were grown at higher temperatures. (3) Acclimation of photosynthesis to the growth temperature seemed to occur so as to maintain photosynthesis activity not at a maximum level but in a certain range at the growth temperatures. (4) Neither sensitivity to high-temperature-induced dissociation of phycobilisomes from the PSII reaction center complexes nor degradation of phycocyanin were altered by changes in the environmental temperature. (5) A close relationship between the viability of cells and the structural changes of plasma membranes (but not the inactivation of photosynthesis) was observed. The denaturation process of PSII complexes and the relationship between the temperature dependence of the growth of Synechocystis PCC6803 cells and that of the photosynthetic activity are also discussed.

Cell Membrane↗